@comment{{This file has been generated by bib2bib 1.97}}
@comment{{Command line: bib2bib ../bibli.bib -c 'subject:"sirna" or keywords:"sirna"' -ob tmp.bib}}
@article{Amarzguioui2004algorithm,
author = {Amarzguioui, M. and Prydz, H.},
title = {An algorithm for selection of functional si{RNA} sequences.},
journal = {Biochem. {B}iophys. {R}es. {C}ommun.},
year = {2004},
volume = {316},
pages = {1050-8},
number = {4},
month = {Apr},
abstract = {Randomly designed si{RNA} targeting different positions within the
same m{RNA} display widely differing activities. {W}e have performed
a statistical analysis of 46 si{RNA}, identifying various features
of the 19bp duplex that correlate significantly with functionality
at the 70\% knockdown level and verified these results against an
independent data set of 34 si{RNA} recently reported by others. {F}eatures
that consistently correlated positively with functionality across
the two data sets included an asymmetry in the stability of the duplex
ends (measured as the {A}/{U} differential of the three terminal
basepairs at either end of the duplex) and the motifs {S}1, {A}6,
and {W}19. {T}he presence of the motifs {U}1 or {G}19 was associated
with lack of functionality. {A} selection algorithm based on these
findings strongly differentiated between the two functional groups
of si{RNA} in both data sets and proved highly effective when used
to design si{RNA} targeting new endogenous human genes.},
doi = {10.1016/j.bbrc.2004.02.157},
keywords = {sirna},
pii = {S0006291X04004425},
url = {http://dx.doi.org/10.1016/j.bbrc.2004.02.157}
}
@article{Ameres2007Molecular,
author = {Stefan Ludwig Ameres and Javier Martinez and Renée Schroeder},
title = {Molecular basis for target RNA recognition and cleavage by human
RISC.},
journal = {Cell},
year = {2007},
volume = {130},
pages = {101--112},
number = {1},
month = {Jul},
abstract = {The RNA-Induced Silencing Complex (RISC) is a ribonucleoprotein particle
composed of a single-stranded short interfering RNA (siRNA) and an
endonucleolytically active Argonaute protein, capable of cleaving
mRNAs complementary to the siRNA. The mechanism by which RISC cleaves
a target RNA is well understood, however it remains enigmatic how
RISC finds its target RNA. Here, we show, both in vitro and in vivo,
that the accessibility of the target site correlates directly with
the efficiency of cleavage, demonstrating that RISC is unable to
unfold structured RNA. In the course of target recognition, RISC
transiently contacts single-stranded RNA nonspecifically and promotes
siRNA-target RNA annealing. Furthermore, the 5' part of the siRNA
within RISC creates a thermodynamic threshold that determines the
stable association of RISC and the target RNA. We therefore provide
mechanistic insights by revealing features of RISC and target RNAs
that are crucial to achieve efficiency and specificity in RNA interference.},
doi = {10.1016/j.cell.2007.04.037},
pdf = {../local/Ameres2007Molecular.pdf},
file = {Ameres2007Molecular.pdf:Ameres2007Molecular.pdf:PDF},
institution = {Max F. Perutz Laboratories, University of Vienna, Vienna, Austria.},
keywords = {sirna},
language = {eng},
medline-pst = {ppublish},
owner = {jp},
pii = {S0092-8674(07)00583-1},
pmid = {17632058},
timestamp = {2009.10.28},
url = {http://dx.doi.org/10.1016/j.cell.2007.04.037}
}
@article{Baek2008impact,
author = {Daehyun Baek and Judit Villén and Chanseok Shin and Fernando D Camargo
and Steven P Gygi and David P Bartel},
title = {The impact of microRNAs on protein output.},
journal = {Nature},
year = {2008},
volume = {455},
pages = {64--71},
number = {7209},
month = {Sep},
abstract = {MicroRNAs are endogenous approximately 23-nucleotide RNAs that can
pair to sites in the messenger RNAs of protein-coding genes to downregulate
the expression from these messages. MicroRNAs are known to influence
the evolution and stability of many mRNAs, but their global impact
on protein output had not been examined. Here we use quantitative
mass spectrometry to measure the response of thousands of proteins
after introducing microRNAs into cultured cells and after deleting
mir-223 in mouse neutrophils. The identities of the responsive proteins
indicate that targeting is primarily through seed-matched sites located
within favourable predicted contexts in 3' untranslated regions.
Hundreds of genes were directly repressed, albeit each to a modest
degree, by individual microRNAs. Although some targets were repressed
without detectable changes in mRNA levels, those translationally
repressed by more than a third also displayed detectable mRNA destabilization,
and, for the more highly repressed targets, mRNA destabilization
usually comprised the major component of repression. The impact of
microRNAs on the proteome indicated that for most interactions microRNAs
act as rheostats to make fine-scale adjustments to protein output.},
doi = {10.1038/nature07242},
pdf = {../local/Baek2008impact.pdf},
file = {Baek2008impact.pdf:Baek2008impact.pdf:PDF},
institution = {Whitehead Institute for Biomedical Research, 9 Cambridge Center,
Cambridge, Massachusetts 02142, USA.},
keywords = {sirna},
language = {eng},
medline-pst = {ppublish},
owner = {jp},
pii = {nature07242},
pmid = {18668037},
timestamp = {2009.10.28},
url = {http://dx.doi.org/10.1038/nature07242}
}
@article{Bartel2004MicroRNAs,
author = {David P Bartel},
title = {MicroRNAs: genomics, biogenesis, mechanism, and function.},
journal = {Cell},
year = {2004},
volume = {116},
pages = {281--297},
number = {2},
month = {Jan},
abstract = {MicroRNAs (miRNAs) are endogenous approximately 22 nt RNAs that can
play important regulatory roles in animals and plants by targeting
mRNAs for cleavage or translational repression. Although they escaped
notice until relatively recently, miRNAs comprise one of the more
abundant classes of gene regulatory molecules in multicellular organisms
and likely influence the output of many protein-coding genes.},
pdf = {../local/Bartel2004MicroRNAs.pdf},
file = {Bartel2004MicroRNAs.pdf:Bartel2004MicroRNAs.pdf:PDF},
institution = {Whitehead Institute for Biomedical Research, 9 Cambridge Center,
Cambridge, MA 02142, USA. dbartel@wi.mit.edu},
keywords = {sirna},
language = {eng},
medline-pst = {ppublish},
owner = {jp},
pii = {S0092867404000455},
pmid = {14744438},
timestamp = {2009.10.28}
}
@article{Boese2005Mechanistic,
author = {Boese, Q. and Leake, D. and Reynolds, A. and Read, S. and Scaringe,
S. A. and Marshall, W. S. and Khvorova, A.},
title = {Mechanistic insights aid computational short interfering {RNA} design.},
journal = {Methods {E}nzymol.},
year = {2005},
volume = {392},
pages = {73-96},
abstract = {R{NA} interference is widely recognized for its utility as a functional
genomics tool. {I}n the absence of reliable target site selection
tools, however, the impact of {RNA} interference ({RNA}i) may be
diminished. {T}he primary determinants of silencing are influenced
by highly coordinated {RNA}-protein interactions that occur throughout
the {RNA}i process, including short interfering {RNA} (si{RNA}) binding
and unwinding followed by target recognition, cleavage, and subsequent
product release. {R}ecently developed strategies for identification
of functional si{RNA}s reveal that thermodynamic and si{RNA} sequence-specific
properties are crucial to predict functional duplexes ({K}hvorova
et al., 2003; {R}eynolds et al., 2004; {S}chwarz et al., 2003). {A}dditional
assessments of si{RNA} specificity reveal that more sophisticated
sequence comparison tools are also required to minimize potential
off-target effects ({J}ackson et al., 2003; {S}emizarov et al., 2003).
{T}his chapter reviews the biological basis for current computational
design tools and how best to utilize and assess their predictive
capabilities for selecting functional and specific si{RNA}s.},
doi = {10.1016/S0076-6879(04)92005-8},
keywords = {sirna},
pii = {S0076687904920058},
url = {http://dx.doi.org/10.1016/S0076-6879(04)92005-8}
}
@article{Brennecke2005Principles,
author = {Julius Brennecke and Alexander Stark and Robert B Russell and Stephen
M Cohen},
title = {Principles of microRNA-target recognition.},
journal = {PLoS Biol},
year = {2005},
volume = {3},
pages = {e85},
number = {3},
month = {Mar},
abstract = {MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression
in plants and animals. Although their biological importance has become
clear, how they recognize and regulate target genes remains less
well understood. Here, we systematically evaluate the minimal requirements
for functional miRNA-target duplexes in vivo and distinguish classes
of target sites with different functional properties. Target sites
can be grouped into two broad categories. 5' dominant sites have
sufficient complementarity to the miRNA 5' end to function with little
or no support from pairing to the miRNA 3' end. Indeed, sites with
3' pairing below the random noise level are functional given a strong
5' end. In contrast, 3' compensatory sites have insufficient 5' pairing
and require strong 3' pairing for function. We present examples and
genome-wide statistical support to show that both classes of sites
are used in biologically relevant genes. We provide evidence that
an average miRNA has approximately 100 target sites, indicating that
miRNAs regulate a large fraction of protein-coding genes and that
miRNA 3' ends are key determinants of target specificity within miRNA
families.},
doi = {10.1371/journal.pbio.0030085},
institution = {European Molecular Biology Laboratory, Heidelberg, Germany.},
keywords = {sirna},
language = {eng},
medline-pst = {ppublish},
owner = {jp},
pmid = {15723116},
timestamp = {2009.10.28},
url = {http://dx.doi.org/10.1371/journal.pbio.0030085}
}
@article{Brodersen2009Revisiting,
author = {Peter Brodersen and Olivier Voinnet},
title = {Revisiting the principles of microRNA target recognition and mode
of action.},
journal = {Nat Rev Mol Cell Biol},
year = {2009},
volume = {10},
pages = {141--148},
number = {2},
month = {Feb},
abstract = {MicroRNAs (miRNAs) are fundamental regulatory elements of animal and
plant gene expression. Although rapid progress in our understanding
of miRNA biogenesis has been achieved by experimentation, computational
approaches have also been influential in determining the general
principles that are thought to govern miRNA target recognition and
mode of action. We discuss how these principles are being progressively
challenged by genetic and biochemical studies. In addition, we discuss
the role of target-site-specific endonucleolytic cleavage, which
is the hallmark of experimental RNA interference and a mechanism
that is used by plant miRNAs and a few animal miRNAs. Generally thought
to be merely a degradation mechanism, we propose that this might
also be a biogenesis mechanism for biologically functional, non-coding
RNA fragments.},
doi = {10.1038/nrm2619},
pdf = {../local/Brodersen2009Revisiting.pdf},
file = {Brodersen2009Revisiting.pdf:Brodersen2009Revisiting.pdf:PDF},
institution = {Institut de Biologie Moléculaire des Plantes, Centre National de
la Recherche Scientifique, 12 rue du Général Zimmer, 67084 Strasbourg
Cedex, France. peter.brodersen@ibmp-ulp.u-strasbg.fr},
keywords = {sirna},
language = {eng},
medline-pst = {ppublish},
owner = {jp},
pii = {nrm2619},
pmid = {19145236},
timestamp = {2009.10.28},
url = {http://dx.doi.org/10.1038/nrm2619}
}
@article{Caplen2001Specific,
author = {Caplen, N. J. and Parrish, S. and Imani, F. and Fire, A. and Morgan,
R. A.},
title = {{S}pecific inhibition of gene expression by small double-stranded
{RNA}s in invertebrate and vertebrate systems.},
journal = {Proc. Natl. Acad. Sci. USA},
year = {2001},
volume = {98},
pages = {9742--9747},
number = {17},
month = {Aug},
abstract = {Short interfering RNAs (siRNAs) are double-stranded RNAs of approximately
21-25 nucleotides that have been shown to function as key intermediaries
in triggering sequence-specific RNA degradation during posttranscriptional
gene silencing in plants and RNA interference in invertebrates. siRNAs
have a characteristic structure, with 5'-phosphate/3'-hydroxyl ends
and a 2-base 3' overhang on each strand of the duplex. In this study,
we present data that synthetic siRNAs can induce gene-specific inhibition
of expression in Caenorhabditis elegans and in cell lines from humans
and mice. In each case, the interference by siRNAs was superior to
the inhibition of gene expression mediated by single-stranded antisense
oligonucleotides. The siRNAs seem to avoid the well documented nonspecific
effects triggered by longer double-stranded RNAs in mammalian cells.
These observations may open a path toward the use of siRNAs as a
reverse genetic and therapeutic tool in mammalian cells.},
doi = {10.1073/pnas.171251798},
pdf = {../local/Caplen2001Specific.pdf},
file = {Caplen2001Specific.pdf:Caplen2001Specific.pdf:PDF},
keywords = {sirna},
owner = {vert},
pii = {171251798},
pmid = {11481446},
timestamp = {2006.03.28},
url = {http://dx.doi.org/10.1073/pnas.171251798}
}
@article{Chalk2004Improved,
author = {Chalk, A. M. and Wahlestedt, C. and Sonnhammer, E. L. L.},
title = {Improved and automated prediction of effective si{RNA}.},
journal = {Biochem. {B}iophys. {R}es. {C}ommun.},
year = {2004},
volume = {319},
pages = {264-74},
number = {1},
month = {Jun},
abstract = {Short interfering {RNA}s are used in functional genomics studies to
knockdown a single gene in a reversible manner. {T}he results of
si{RNA} experiments are highly dependent on the choice of si{RNA}
sequence. {I}n order to evaluate si{RNA} design rules, we collected
a database of 398 si{RNA}s of known efficacy from 92 genes. {W}e
used this database to evaluate previously proposed rules from smaller
datasets, and to find a new set of rules that are optimal for the
entire database. {W}e also trained a regression tree with full cross-validation.
{I}t was however difficult to obtain the same precision as methods
previously tested on small datasets from one or two genes. {W}e show
that those methods are overfitting as they work poorly on independent
validation datasets from multiple genes. {O}ur new design rules can
predict si{RNA}s with efficacy >/= 50\% in 91\% of cases, and with
efficacy >/=90\% in 52\% of cases, which is more than a twofold improvement
over random selection. {S}oftware for designing si{RNA}s is available
online via a web server at or as a standalone version for high-throughput
applications.},
doi = {10.1016/j.bbrc.2004.04.181},
pdf = {../local/Chalk2004Improved.pdf},
file = {Chalk2004Improved.pdf:local/Chalk2004Improved.pdf:PDF},
keywords = {sirna},
pii = {S0006291X04009374},
url = {http://dx.doi.org/10.1016/j.bbrc.2004.04.181}
}
@article{Chalk2005siRNAdb,
author = {Chalk, A. M. and Warfinge, R. E. and Georgii-Hemming, P. and Sonnhammer,
E. L. L.},
title = {si{RNA}db: a database of si{RNA} sequences.},
journal = {Nucleic Acids Res.},
year = {2005},
volume = {33},
pages = {D131--D134},
number = {Database issue},
month = {Jan},
abstract = {Short interfering RNAs (siRNAs) are a popular method for gene-knockdown,
acting by degrading the target mRNA. Before performing experiments
it is invaluable to locate and evaluate previous knockdown experiments
for the gene of interest. The siRNA database provides a gene-centric
view of siRNA experimental data, including siRNAs of known efficacy
and siRNAs predicted to be of high efficacy by a combination of methods.
Linked to these sequences is information such as siRNA thermodynamic
properties and the potential for sequence-specific off-target effects.
The database enables the user to evaluate an siRNA's potential for
inhibition and non-specific effects. The database is available at
http://siRNA.cgb.ki.se.},
doi = {10.1093/nar/gki136},
pdf = {../local/Chalk2005siRNAdb.pdf},
file = {Chalk2005siRNAdb.pdf:Chalk2005siRNAdb.pdf:PDF},
keywords = {sirna},
owner = {vert},
pii = {33/suppl_1/D131},
pmid = {15608162},
timestamp = {2006.03.28},
url = {http://dx.doi.org/10.1093/nar/gki136}
}
@article{Cogoni1996Transgene,
author = {Cogoni, C. and Irelan, J. T. and Schumacher, M. and Schmidhauser,
T. J. and Selker, E. U. and Macino, G.},
title = {{T}ransgene silencing of the al-1 gene in vegetative cells of {N}eurospora
is mediated by a cytoplasmic effector and does not depend on {DNA}-{DNA}
interactions or {DNA} methylation.},
journal = {EMBO J.},
year = {1996},
volume = {15},
pages = {3153--3163},
number = {12},
month = {Jun},
abstract = {The molecular mechanisms involved in transgene-induced gene silencing
('quelling') in Neurospora crassa were investigated using the carotenoid
biosynthetic gene albino-1 (al-1) as a visual marker. Deletion derivatives
of the al-1 gene showed that a transgene must contain at least approximately
132 bp of sequences homologous to the transcribed region of the native
gene in order to induce quelling. Transgenes containing only al-1
promoter sequences do not cause quelling. Specific sequences are
not required for gene silencing, as different regions of the al-1
gene produced quelling. A mutant defective in cytosine methylation
(dim-2) exhibited normal frequencies and degrees of silencing, indicating
that cytosine methylation is not responsible for quelling, despite
the fact that methylation of transgene sequences frequently is correlated
with silencing. Silencing was shown to be a dominant trait, operative
in heterokaryotic strains containing a mixture of transgenic and
non-transgenic nuclei. This result indicates that a diffusable, trans-acting
molecule is involved in quelling. A transgene-derived, sense RNA
was detected in quelled strains and was found to be absent in their
revertants. These data are consistent with a model in which an RNA-DNA
or RNA-RNA interaction is involved in transgene-induced gene silencing
in Neurospora.},
pdf = {../local/Cogoni1996Transgene.pdf},
file = {Cogoni1996Transgene.pdf:Cogoni1996Transgene.pdf:PDF},
keywords = {sirna},
owner = {vert},
pmid = {8670816},
timestamp = {2006.03.28},
url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC450258}
}
@article{Didiano2008Molecular,
author = {Dominic Didiano and Oliver Hobert},
title = {Molecular architecture of a miRNA-regulated 3' UTR.},
journal = {RNA},
year = {2008},
volume = {14},
pages = {1297--1317},
number = {7},
month = {Jul},
abstract = {Animal genomes contain hundreds of microRNAs (miRNAs), small regulatory
RNAs that control gene expression by binding to complementary sites
in target mRNAs. Some rules that govern miRNA/target interaction
have been elucidated but their general applicability awaits further
experimentation on a case-by-case basis. We use here an assay system
in transgenic nematodes to analyze the interaction of the Caenorhabditis
elegans lsy-6 miRNA with 3' UTR sequences. In contrast to many previously
described assay systems used to analyze miRNA/target interactions,
our assay system operates within the cellular context in which lsy-6
normally functions, a single neuron in the nervous system of C. elegans.
Through extensive mutational analysis, we define features in the
known and experimentally validated target of lsy-6, the 3' UTR of
the cog-1 homeobox gene, that are required for a functional miRNA/target
interaction. We describe that both in the context of the cog-1 3'
UTR and in the context of heterologous 3' UTRs, one or more seed
matches are not a reliable predictor for a functional miRNA/target
interaction. We rather find that two nonsequence specific contextual
features beyond miRNA target sites are critical determinants of miRNA-mediated
3' UTR regulation. The contextual features reside 3' of lsy-6 binding
sites in the 3' UTR and act in a combinatorial manner; mutation of
each results in limited defects in 3' UTR regulation, but a combinatorial
deletion results in complete loss of 3' UTR regulation. Together
with two lsy-6 sites, these two contextual features are capable of
imparting regulation on a heterologous 3' UTR. Moreover, the contextual
features need to be present in a specific configuration relative
to miRNA binding sites and could either represent protein binding
sites or provide an appropriate structural context. We conclude that
a given target site resides in a 3' UTR context that evolved beyond
target site complementarity to support regulation by a specific miRNA.
The large number of 3' UTRs that we analyzed in this study will also
be useful to computational biologists in designing the next generation
of miRNA/target prediction algorithms.},
doi = {10.1261/rna.1082708},
pdf = {../local/Didiano2008Molecular.pdf},
file = {Didiano2008Molecular.pdf:Didiano2008Molecular.pdf:PDF},
institution = {Department of Biochemistry and Molecular Biophysics, Howard Hughes
Medical Institute, Columbia University Medical Center, New York,
New York 10032, USA.},
keywords = {sirna},
language = {eng},
medline-pst = {ppublish},
owner = {jp},
pii = {rna.1082708},
pmid = {18463285},
timestamp = {2009.10.28},
url = {http://dx.doi.org/10.1261/rna.1082708}
}
@article{Didiano2006Perfect,
author = {Dominic Didiano and Oliver Hobert},
title = {Perfect seed pairing is not a generally reliable predictor for miRNA-target
interactions.},
journal = {Nat Struct Mol Biol},
year = {2006},
volume = {13},
pages = {849--851},
number = {9},
month = {Sep},
abstract = {We use Caenorhabditis elegans to test proposed general rules for microRNA
(miRNA)-target interactions. We show that G.U base pairing is tolerated
in the 'seed' region of the lsy-6 miRNA interaction with its in vivo
target cog-1, and that 6- to 8-base-pair perfect seed pairing is
not a generally reliable predictor for an interaction of lsy-6 with
a 3' untranslated region (UTR). Rather, lsy-6 can functionally interact
with its target site only in specific 3' UTR contexts. Our findings
illustrate the difficulty of establishing generalizable rules of
miRNA-target interactions.},
doi = {10.1038/nsmb1138},
pdf = {../local/Didiano2006Perfect.pdf},
file = {Didiano2006Perfect.pdf:Didiano2006Perfect.pdf:PDF},
institution = {Department of Biochemistry and Molecular Biophysics, Columbia University
Medical Center, Howard Hughes Medical Institute, 701 W. 168th Street,
New York, New York 10032, USA.},
keywords = {sirna},
language = {eng},
medline-pst = {ppublish},
owner = {jp},
pii = {nsmb1138},
pmid = {16921378},
timestamp = {2009.10.28},
url = {http://dx.doi.org/10.1038/nsmb1138}
}
@article{Ding2004Sfold,
author = {Ding, Y. and Yu, C. Chan and Lawrence, C. E.},
title = {{S}fold web server for statistical folding and rational design of
nucleic acids.},
journal = {Nucleic Acids Res.},
year = {2004},
volume = {32},
pages = {W135--W141},
number = {Web Server issue},
month = {Jul},
abstract = {The Sfold web server provides user-friendly access to Sfold, a recently
developed nucleic acid folding software package, via the World Wide
Web (WWW). The software is based on a new statistical sampling paradigm
for the prediction of RNA secondary structure. One of the main objectives
of this software is to offer computational tools for the rational
design of RNA-targeting nucleic acids, which include small interfering
RNAs (siRNAs), antisense oligonucleotides and trans-cleaving ribozymes
for gene knock-down studies. The methodology for siRNA design is
based on a combination of RNA target accessibility prediction, siRNA
duplex thermodynamic properties and empirical design rules. Our approach
to target accessibility evaluation is an original extension of the
underlying RNA folding algorithm to account for the likely existence
of a population of structures for the target mRNA. In addition to
the application modules Sirna, Soligo and Sribo for siRNAs, antisense
oligos and ribozymes, respectively, the module Srna offers comprehensive
features for statistical representation of sampled structures. Detailed
output in both graphical and text formats is available for all modules.
The Sfold server is available at http://sfold.wadsworth.org and http://www.bioinfo.rpi.edu/applications/sfold.},
doi = {10.1093/nar/gkh449},
keywords = {sirna},
owner = {vert},
pii = {32/suppl_2/W135},
pmid = {15215366},
timestamp = {2006.03.28},
url = {http://dx.doi.org/10.1093/nar/gkh449}
}
@article{Elbashir2001Duplexes,
author = {Elbashir, S. M. and Harborth, J. and Lendeckel, W. and Yalcin, A.
and Weber, K. and Tuschl, T.},
title = {{D}uplexes of 21-nucleotide {RNA}s mediate {RNA} interference in
cultured mammalian cells.},
journal = {Nature},
year = {2001},
volume = {411},
pages = {494--498},
number = {6836},
month = {May},
abstract = {RNA interference (RNAi) is the process of sequence-specific, post-transcriptional
gene silencing in animals and plants, initiated by double-stranded
RNA (dsRNA) that is homologous in sequence to the silenced gene.
The mediators of sequence-specific messenger RNA degradation are
21- and 22-nucleotide small interfering RNAs (siRNAs) generated by
ribonuclease III cleavage from longer dsRNAs. Here we show that 21-nucleotide
siRNA duplexes specifically suppress expression of endogenous and
heterologous genes in different mammalian cell lines, including human
embryonic kidney (293) and HeLa cells. Therefore, 21-nucleotide siRNA
duplexes provide a new tool for studying gene function in mammalian
cells and may eventually be used as gene-specific therapeutics.},
doi = {10.1038/35078107},
pdf = {../local/Elbashir2001Duplexes.pdf},
file = {Elbashir2001Duplexes.pdf:Elbashir2001Duplexes.pdf:PDF},
keywords = {sirna},
owner = {vert},
pii = {35078107},
pmid = {11373658},
timestamp = {2006.03.28},
url = {http://dx.doi.org/10.1038/35078107}
}
@article{Elbashir2001RNA,
author = {Elbashir, S. M. and Lendeckel, W. and Tuschl, T.},
title = {R{NA} interference is mediated by 21- and 22-nucleotide {RNA}s.},
journal = {Genes {D}ev.},
year = {2001},
volume = {15},
pages = {188-200},
number = {2},
month = {Jan},
abstract = {Double-stranded {RNA} (ds{RNA}) induces sequence-specific posttranscriptional
gene silencing in many organisms by a process known as {RNA} interference
({RNA}i). {U}sing a {D}rosophila in vitro system, we demonstrate
that 21- and 22-nt {RNA} fragments are the sequence-specific mediators
of {RNA}i. {T}he short interfering {RNA}s (si{RNA}s) are generated
by an {RN}ase {III}-like processing reaction from long ds{RNA}. {C}hemically
synthesized si{RNA} duplexes with overhanging 3' ends mediate efficient
target {RNA} cleavage in the lysate, and the cleavage site is located
near the center of the region spanned by the guiding si{RNA}. {F}urthermore,
we provide evidence that the direction of ds{RNA} processing determines
whether sense or antisense target {RNA} can be cleaved by the si{RNA}-protein
complex.},
keywords = {sirna}
}
@article{Eulalio2008Getting,
author = {Ana Eulalio and Eric Huntzinger and Elisa Izaurralde},
title = {Getting to the root of miRNA-mediated gene silencing.},
journal = {Cell},
year = {2008},
volume = {132},
pages = {9--14},
number = {1},
month = {Jan},
abstract = {MicroRNAs are approximately 22 nucleotide-long RNAs that silence gene
expression posttranscriptionally by binding to the 3' untranslated
regions of target mRNAs. Although much is known about their biogenesis
and biological functions, the mechanisms allowing miRNAs to silence
gene expression in animal cells are still under debate. Here, we
discuss current models for miRNA-mediated gene silencing and formulate
a hypothesis to reconcile differences.},
doi = {10.1016/j.cell.2007.12.024},
institution = {Max-Planck-Institute for Developmental Biology, Spemannstrasse 35,
D-72076 Tübingen, Germany.},
keywords = {sirna},
language = {eng},
medline-pst = {ppublish},
owner = {jp},
pii = {S0092-8674(07)01697-2},
pmid = {18191211},
timestamp = {2009.10.28},
url = {http://dx.doi.org/10.1016/j.cell.2007.12.024}
}
@article{Fire1998Potent,
author = {Fire, A. and Xu, S. and Montgomery, M. K. and Kostas, S. A. and Driver,
S. E. and Mello, C. C.},
title = {{P}otent and specific genetic interference by double-stranded {RNA}
in {C}aenorhabditis elegans.},
journal = {Nature},
year = {1998},
volume = {391},
pages = {806--811},
number = {6669},
month = {Feb},
abstract = {Experimental introduction of RNA into cells can be used in certain
biological systems to interfere with the function of an endogenous
gene. Such effects have been proposed to result from a simple antisense
mechanism that depends on hybridization between the injected RNA
and endogenous messenger RNA transcripts. RNA interference has been
used in the nematode Caenorhabditis elegans to manipulate gene expression.
Here we investigate the requirements for structure and delivery of
the interfering RNA. To our surprise, we found that double-stranded
RNA was substantially more effective at producing interference than
was either strand individually. After injection into adult animals,
purified single strands had at most a modest effect, whereas double-stranded
mixtures caused potent and specific interference. The effects of
this interference were evident in both the injected animals and their
progeny. Only a few molecules of injected double-stranded RNA were
required per affected cell, arguing against stochiometric interference
with endogenous mRNA and suggesting that there could be a catalytic
or amplification component in the interference process.},
doi = {10.1038/35888},
pdf = {../local/Fire1998Potent.pdf},
file = {Fire1998Potent.pdf:Fire1998Potent.pdf:PDF},
keywords = {sirna},
owner = {vert},
pmid = {9486639},
timestamp = {2006.03.28},
url = {http://dx.doi.org/10.1038/35888}
}
@article{Gong2004Picking,
author = {Gong, D. and Ferrell, J. E.},
title = {Picking a winner: new mechanistic insights into the design of effective
si{RNA}s.},
journal = {Trends {B}iotechnol.},
year = {2004},
volume = {22},
pages = {451-4},
number = {9},
month = {Sep},
abstract = {Recent work has shown that the efficacy of a small interfering {RNA}
(si{RNA}) for silencing gene expression is a function of how easy
it is to unwind the si{RNA} from the 5'-antisense end. {B}ased on
these insights, one group has designed an algorithm that substantially
improves the odds of picking an effective si{RNA}, and two groups
have shown that 'forked' or 'frayed' si{RNA}s, which should be easier
to unwind from the 5'-antisense end, are more effective than conventional
si{RNA}s. {T}hese strategies represent important steps towards the
rational design of effective si{RNA}s.},
doi = {10.1016/j.tibtech.2004.07.008},
keywords = {sirna},
pii = {S0167-7799(04)00201-X},
url = {http://dx.doi.org/10.1016/j.tibtech.2004.07.008}
}
@article{Grimson2007MicroRNA,
author = {Andrew Grimson and Kyle Kai-How Farh and Wendy K Johnston and Philip
Garrett-Engele and Lee P Lim and David P Bartel},
title = {MicroRNA targeting specificity in mammals: determinants beyond seed
pairing.},
journal = {Mol Cell},
year = {2007},
volume = {27},
pages = {91--105},
number = {1},
month = {Jul},
abstract = {Mammalian microRNAs (miRNAs) pair to 3'UTRs of mRNAs to direct their
posttranscriptional repression. Important for target recognition
are approximately 7 nt sites that match the seed region of the miRNA.
However, these seed matches are not always sufficient for repression,
indicating that other characteristics help specify targeting. By
combining computational and experimental approaches, we uncovered
five general features of site context that boost site efficacy: AU-rich
nucleotide composition near the site, proximity to sites for coexpressed
miRNAs (which leads to cooperative action), proximity to residues
pairing to miRNA nucleotides 13-16, positioning within the 3'UTR
at least 15 nt from the stop codon, and positioning away from the
center of long UTRs. A model combining these context determinants
quantitatively predicts site performance both for exogenously added
miRNAs and for endogenous miRNA-message interactions. Because it
predicts site efficacy without recourse to evolutionary conservation,
the model also identifies effective nonconserved sites and siRNA
off-targets.},
doi = {10.1016/j.molcel.2007.06.017},
pdf = {../local/Grimson2007MicroRNA.pdf},
file = {Grimson2007MicroRNA.pdf:Grimson2007MicroRNA.pdf:PDF},
institution = {Howard Hughes Medical Institute, Massachusetts Institute of Technology,
Cambridge, MA 02139, USA.},
keywords = {sirna},
language = {eng},
medline-pst = {ppublish},
owner = {jp},
pii = {S1097-2765(07)00407-8},
pmid = {17612493},
timestamp = {2009.10.28},
url = {http://dx.doi.org/10.1016/j.molcel.2007.06.017}
}
@article{Haley2004Kinetic,
author = {Haley, B. and Zamore, P. D.},
title = {{K}inetic analysis of the {RNA}i enzyme complex.},
journal = {Nat. Struct. Mol. Biol.},
year = {2004},
volume = {11},
pages = {599--606},
number = {7},
month = {Jul},
abstract = {The siRNA-directed ribonucleoprotein complex, RISC, catalyzes target
RNA cleavage in the RNA interference pathway. Here, we show that
siRNA-programmed RISC is a classical Michaelis-Menten enzyme in the
presence of ATP. In the absence of ATP, the rate of multiple rounds
of catalysis is limited by release of the cleaved products from the
enzyme. Kinetic analysis suggests that different regions of the siRNA
play distinct roles in the cycle of target recognition, cleavage,
and product release. Bases near the siRNA 5' end disproportionately
contribute to target RNA-binding energy, whereas base pairs formed
by the central and 3' regions of the siRNA provide a helical geometry
required for catalysis. Finally, the position of the scissile phosphate
on the target RNA seems to be determined during RISC assembly, before
the siRNA encounters its RNA target.},
doi = {10.1038/nsmb780},
pdf = {../local/Haley2004Kinetic.pdf},
file = {Haley2004Kinetic.pdf:Haley2004Kinetic.pdf:PDF},
keywords = {sirna},
owner = {vert},
pii = {nsmb780},
pmid = {15170178},
timestamp = {2006.04.27},
url = {http://dx.doi.org/10.1038/nsmb780}
}
@article{Hall2004Unravelling,
author = {Hall, J.},
title = {Unravelling the general properties of si{RNA}s: strength in numbers
and lessons from the past.},
journal = {Nat. {R}ev. {G}enet.},
year = {2004},
volume = {5},
pages = {552-7},
number = {7},
month = {Jul},
doi = {10.1038/nrg1382},
pdf = {../local/Hall2004Unravelling.pdf},
file = {Hall2004Unravelling.pdf:local/Hall2004Unravelling.pdf:PDF},
keywords = {sirna},
pii = {nrg1382},
url = {http://dx.doi.org/10.1038/nrg1382}
}
@article{Hannon2004Unlocking,
author = {Hannon, G. J. and Rossi, J. J.},
title = {Unlocking the potential of the human genome with {RNA} interference.},
journal = {Nature},
year = {2004},
volume = {431},
pages = {371-8},
number = {7006},
month = {Sep},
abstract = {The discovery of {RNA} interference ({RNA}i) may well be one of the
transforming events in biology in the past decade. {RNA}i can result
in gene silencing or even in the expulsion of sequences from the
genome. {H}arnessed as an experimental tool, {RNA}i has revolutionized
approaches to decoding gene function. {I}t also has the potential
to be exploited therapeutically, and clinical trials to test this
possibility are already being planned.},
doi = {10.1038/nature02870},
pdf = {../local/Hannon2004Unlocking.pdf},
file = {Hannon2004Unlocking.pdf:local/Hannon2004Unlocking.pdf:PDF},
keywords = {sirna},
pii = {nature02870},
url = {http://dx.doi.org/10.1038/nature02870}
}
@article{Holen2002Positional,
author = {Holen, T. and Amarzguioui, M. and Wiiger, M. T. and Babaie, E. and
Prydz, H.},
title = {{P}ositional effects of short interfering {RNA}s targeting the human
coagulation trigger {T}issue {F}actor.},
journal = {Nucleic Acids Res.},
year = {2002},
volume = {30},
pages = {1757--1766},
number = {8},
month = {Apr},
abstract = {Chemically synthesised 21-23 bp double-stranded short interfering
RNAs (siRNA) can induce sequence-specific post-transcriptional gene
silencing, in a process termed RNA interference (RNAi). In the present
study, several siRNAs synthesised against different sites on the
same target mRNA (human Tissue Factor) demonstrated striking differences
in silencing efficiency. Only a few of the siRNAs resulted in a significant
reduction in expression, suggesting that accessible siRNA target
sites may be rare in some human mRNAs. Blocking of the 3'-OH with
FITC did not reduce the effect on target mRNA. Mutations in the siRNAs
relative to target mRNA sequence gradually reduced, but did not abolish
mRNA depletion. Inactive siRNAs competed reversibly with active siRNAs
in a sequence-independent manner. Several lines of evidence suggest
the existence of a near equilibrium kinetic balance between mRNA
production and siRNA-mediated mRNA depletion. The silencing effect
was transient, with the level of mRNA recovering fully within 4-5
days, suggesting absence of a propagative system for RNAi in humans.
Finally, we observed 3' mRNA cleavage fragments resulting from the
action of the most effective siRNAs. The depletion rate-dependent
appearance of these fragments argues for the existence of a two-step
mRNA degradation mechanism.},
keywords = {sirna},
owner = {vert},
pmid = {11937629},
timestamp = {2006.03.28}
}
@article{Hsieh2004library,
author = {Hsieh, A. C. and Bo, R. and Manola, J. and Vazquez, F. and Bare,
O. and Khvorova, A. and Scaringe, S. and Sellers, W. R.},
title = {A library of si{RNA} duplexes targeting the phosphoinositide 3-kinase
pathway: determinants of gene silencing for use in cell-based screens.},
journal = {Nucleic {A}cids {R}es.},
year = {2004},
volume = {32},
pages = {893-901},
number = {3},
abstract = {Gene silencing through {RNA} interference ({RNA}i) has been established
as a means of conducting reverse genetic studies. {I}n order to better
understand the determinants of short interfering {RNA} (si{RNA})
knockdown for use in high-throughput cell-based screens, 148 si{RNA}
duplexes targeting 30 genes within the {PI}3{K} pathway were selected
and synthesized. {T}he extent of {RNA} knockdown was measured for
22 genes by quantitative real-time {PCR}. {A}nalysis of the parameters
correlating with effective knockdown showed that (i) duplexes targeting
the middle of the coding sequence silenced significantly poorer,
(ii) silencing by duplexes targeting the 3'{UTR} was comparable with
duplexes targeting the coding sequence, (iii) pooling of four or
five duplexes per gene was remarkably efficient in knocking down
gene expression and (iv) among duplexes that achieved a >70\% knockdown
of the m{RNA} there were strong nucleotide preferences at specific
positions, most notably positions 11 ({G} or {C}) and 19 ({T}) of
the si{RNA} duplex. {F}inally, in a proof-of-principle pathway-wide
cell-based genetic screen, conducted to detect negative genetic regulators
of {A}kt {S}473 phosphorylation, both known negative regulators of
this phosphorylation, {PTEN} and {PDK}1, were found. {T}hese data
help to lay the foundation for genome-wide si{RNA} screens in mammalian
cells.},
doi = {10.1093/nar/gkh238},
pdf = {../local/Hsieh2004library.pdf},
file = {Hsieh2004library.pdf:local/Hsieh2004library.pdf:PDF},
keywords = {sirna},
pii = {32/3/893},
url = {http://dx.doi.org/10.1093/nar/gkh238}
}
@article{Huesken2005Design,
author = {Huesken, D. and Lange, J. and Mickanin, C. and Weiler, J. and Asselbergs,
F. and Warner, J. and Meloon, B. and Engel, S. and Rosenberg, A.
and Cohen, D. and Labow, M. and Reinhardt, M. and Natt, F. and Hall,
J.},
title = {Design of a genome-wide si{RNA} library using an artificial neural
network.},
journal = {Nat. {B}iotechnol.},
year = {2005},
volume = {23},
pages = {995-1001},
number = {8},
month = {Aug},
abstract = {The largest gene knock-down experiments performed to date have used
multiple short interfering/short hairpin (si/sh){RNA}s per gene1,
2, 3. {T}o overcome this burden for design of a genome-wide si{RNA}
library, we used the {S}tuttgart {N}eural {N}et {S}imulator to train
algorithms on a data set of 2,182 randomly selected si{RNA}s targeted
to 34 m{RNA} species, assayed through a high-throughput fluorescent
reporter gene system. {T}he algorithm, ({BIOPRED}si), reliably predicted
activity of 249 si{RNA}s of an independent test set ({P}earson coefficient
r = 0.66) and si{RNA}s targeting endogenous genes at m{RNA} and protein
levels. {N}eural networks trained on a complementary 21-nucleotide
(nt) guide sequence were superior to those trained on a 19-nt sequence.
{BIOPRED}si was used in the design of a genome-wide si{RNA} collection
with two potent si{RNA}s per gene. {W}hen this collection of 50,000
si{RNA}s was used to identify genes involved in the cellular response
to hypoxia, two of the most potent hits were the key hypoxia transcription
factors {HIF}1{A} and {ARNT}.},
doi = {10.1038/nbt1118},
pdf = {../local/Huesken2005Design.pdf},
file = {Huesken2005Design.pdf:local/Huesken2005Design.pdf:PDF},
keywords = {sirna},
url = {http://dx.doi.org/10.1038/nbt1118}
}
@article{Huppi2005Defining,
author = {Huppi, K. and Martin, S. E. and Caplen, N. J.},
title = {Defining and assaying {RNA}i in mammalian cells.},
journal = {Mol. {C}ell},
year = {2005},
volume = {17},
pages = {1-10},
number = {1},
month = {Jan},
abstract = {The investigation of protein function through the inhibition of activity
has been critical to our understanding of many normal and abnormal
biological processes. {U}ntil recently, functional inhibition in
biological systems has been induced using a variety of approaches
including small molecule antagonists, antibodies, aptamers, ribozymes,
antisense oligonucleotides or transcripts, morpholinos, dominant-negative
mutants, and knockout transgenic animals. {A}lthough all of these
approaches have made substantial advances in our understanding of
the function of many proteins, a lack of specificity or restricted
applicability has limited their utility. {R}ecently, exploitation
of the naturally occurring posttranscriptional gene silencing mechanism
triggered by double-stranded {RNA} (ds{RNA}), termed {RNA} interference
({RNA}i), has gained much favor as an alternative means for analyzing
gene function. {A}spects of the basic biology of {RNA}i, its application
as a functional genomics tool, and its potential as a therapeutic
approach have been extensively reviewed ({H}annon and {R}ossi, 2004;
{M}eister and {T}uschl, 2004); however, there has been only limited
discussion as to how to design and validate an individual {RNA}i
effector molecule and how to interpret {RNA}i data overall, particularly
with reference to experimentation in mammalian cells. {T}his perspective
will aim to consider some of the issues encountered when conducting
and interpreting {RNA}i experiments in mammalian cells.},
doi = {10.1016/j.molcel.2004.12.017},
keywords = {sirna},
pii = {S1097276504008032},
url = {http://dx.doi.org/10.1016/j.molcel.2004.12.017}
}
@article{Jackson2003Expression,
author = {Jackson, A. L. and Bartz, S. R. and Schelter, J. and Kobayashi, S.
V. and Burchard, J. and Mao, M. and Li, B. and Cavet, G. and Linsley,
P. S.},
title = {Expression profiling reveals off-target gene regulation by {RNA}i.},
journal = {Nat. {B}iotechnol.},
year = {2003},
volume = {21},
pages = {635-7},
number = {6},
month = {Jun},
abstract = {R{NA} interference is thought to require near-identity between the
small interfering {RNA} (si{RNA}) and its cognate m{RNA}. {H}ere,
we used gene expression profiling to characterize the specificity
of gene silencing by si{RNA}s in cultured human cells. {T}ranscript
profiles revealed si{RNA}-specific rather than target-specific signatures,
including direct silencing of nontargeted genes containing as few
as eleven contiguous nucleotides of identity to the si{RNA}. {T}hese
results demonstrate that si{RNA}s may cross-react with targets of
limited sequence similarity.},
doi = {10.1038/nbt831},
keywords = {sirna},
pii = {nbt831},
url = {http://dx.doi.org/10.1038/nbt831}
}
@article{Jackson2004Noise,
author = {Jackson, A. L. and Linsley, P. S.},
title = {Noise amidst the silence: off-target effects of si{RNA}s?},
journal = {Trends {G}enet.},
year = {2004},
volume = {20},
pages = {521-4},
number = {11},
month = {Nov},
abstract = {R{NA} interference ({RNA}i), mediated by short interfering {RNA}s
(si{RNA}s), is widely used to silence gene expression and to define
gene function in mammalian cells. {I}nitially, this gene silencing
via transcript degradation was believed to be exquisitely specific,
requiring near-identity between the si{RNA} and the target m{RNA}.
{H}owever, several recent reports have suggested that non-specific
effects can be induced by si{RNA}s, both at the level of m{RNA} and
protein. {T}hese findings suggest that si{RNA}s can regulate the
expression of unintended targets, and argue for further experiments
on the mechanism and extent of off-target gene regulation(s). {I}n
the meantime, caution is warranted in interpreting gene function
and phenotypes resulting from {RNA}i experiments.},
doi = {10.1016/j.tig.2004.08.006},
keywords = {sirna},
pii = {S0168-9525(04)00240-9},
url = {http://dx.doi.org/10.1016/j.tig.2004.08.006}
}
@article{Jia2006Demonstration,
author = {Jia, P. and Shi, T. and Cai, Y. and Li, Y.},
title = {{D}emonstration of two novel methods for predicting functional si{RNA}
efficiency.},
journal = {BMC Bioinformatics},
year = {2006},
volume = {7},
pages = {271},
abstract = {BACKGROUND: siRNAs are small RNAs that serve as sequence determinants
during the gene silencing process called RNA interference (RNAi).
It is well know that siRNA efficiency is crucial in the RNAi pathway,
and the siRNA efficiency for targeting different sites of a specific
gene varies greatly. Therefore, there is high demand for reliable
siRNAs prediction tools and for the design methods able to pick up
high silencing potential siRNAs. RESULTS: In this paper, two systems
have been established for the prediction of functional siRNAs: (1)
a statistical model based on sequence information and (2) a machine
learning model based on three features of siRNA sequences, namely
binary description, thermodynamic profile and nucleotide composition.
Both of the two methods show high performance on the two datasets
we have constructed for training the model. CONCLUSION: Both of the
two methods studied in this paper emphasize the importance of sequence
information for the prediction of functional siRNAs. The way of denoting
a bio-sequence by binary system in mathematical language might be
helpful in other analysis work associated with fixed-length bio-sequence.},
doi = {10.1186/1471-2105-7-271},
pdf = {../local/Jia2006Demonstration.pdf},
file = {Jia2006Demonstration.pdf:local/Jia2006Demonstration.pdf:PDF},
keywords = {sirna},
pii = {1471-2105-7-271},
pmid = {16729898},
timestamp = {2006.10.12},
url = {http://dx.doi.org/10.1186/1471-2105-7-271}
}
@article{John2004Human,
author = {Bino John and Anton J Enright and Alexei Aravin and Thomas Tuschl
and Chris Sander and Debora S Marks},
title = {Human MicroRNA targets.},
journal = {PLoS Biol},
year = {2004},
volume = {2},
pages = {e363},
number = {11},
month = {Nov},
abstract = {MicroRNAs (miRNAs) interact with target mRNAs at specific sites to
induce cleavage of the message or inhibit translation. The specific
function of most mammalian miRNAs is unknown. We have predicted target
sites on the 3' untranslated regions of human gene transcripts for
all currently known 218 mammalian miRNAs to facilitate focused experiments.
We report about 2,000 human genes with miRNA target sites conserved
in mammals and about 250 human genes conserved as targets between
mammals and fish. The prediction algorithm optimizes sequence complementarity
using position-specific rules and relies on strict requirements of
interspecies conservation. Experimental support for the validity
of the method comes from known targets and from strong enrichment
of predicted targets in mRNAs associated with the fragile X mental
retardation protein in mammals. This is consistent with the hypothesis
that miRNAs act as sequence-specific adaptors in the interaction
of ribonuclear particles with translationally regulated messages.
Overrepresented groups of targets include mRNAs coding for transcription
factors, components of the miRNA machinery, and other proteins involved
in translational regulation, as well as components of the ubiquitin
machinery, representing novel feedback loops in gene regulation.
Detailed information about target genes, target processes, and open-source
software for target prediction (miRanda) is available at http://www.microrna.org.
Our analysis suggests that miRNA genes, which are about 1\% of all
human genes, regulate protein production for 10\% or more of all
human genes.},
doi = {10.1371/journal.pbio.0020363},
pdf = {../local/John2004Human.pdf},
file = {John2004Human.pdf:John2004Human.pdf:PDF},
institution = {Computational Biology Center, Memorial Sloan-Kettering Cancer Center,
New York, New York, USA.},
keywords = {sirna},
language = {eng},
medline-pst = {ppublish},
owner = {jp},
pmid = {15502875},
timestamp = {2009.10.28},
url = {http://dx.doi.org/10.1371/journal.pbio.0020363}
}
@article{Jones-Rhoades2004Computational,
author = {Matthew W Jones-Rhoades and David P Bartel},
title = {Computational identification of plant microRNAs and their targets,
including a stress-induced miRNA.},
journal = {Mol Cell},
year = {2004},
volume = {14},
pages = {787--799},
number = {6},
month = {Jun},
abstract = {MicroRNAs (miRNAs) are approximately 21-nucleotide RNAs, some of which
have been shown to play important gene-regulatory roles during plant
development. We developed comparative genomic approaches to systematically
identify both miRNAs and their targets that are conserved in Arabidopsis
thaliana and rice (Oryza sativa). Twenty-three miRNA candidates,
representing seven newly identified gene families, were experimentally
validated in Arabidopsis, bringing the total number of reported miRNA
genes to 92, representing 22 families. Nineteen newly identified
target candidates were confirmed by detecting mRNA fragments diagnostic
of miRNA-directed cleavage in plants. Overall, plant miRNAs have
a strong propensity to target genes controlling development, particularly
those of transcription factors and F-box proteins. However, plant
miRNAs have conserved regulatory functions extending beyond development,
in that they also target superoxide dismutases, laccases, and ATP
sulfurylases. The expression of miR395, the sulfurylase-targeting
miRNA, increases upon sulfate starvation, showing that miRNAs can
be induced by environmental stress.},
doi = {10.1016/j.molcel.2004.05.027},
pdf = {../local/Jones-Rhoades2004Computational.pdf},
file = {Jones-Rhoades2004Computational.pdf:Jones-Rhoades2004Computational.pdf:PDF},
institution = {Whitehead Institute for Biomedical Research and Department of Biology,
Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge,
MA 02142, USA.},
keywords = {sirna},
language = {eng},
medline-pst = {ppublish},
owner = {jp},
pii = {S1097276504003284},
pmid = {15200956},
timestamp = {2009.10.28},
url = {http://dx.doi.org/10.1016/j.molcel.2004.05.027}
}
@incollection{Jorgensen2003Sense,
author = {Jorgensen, R. A.},
title = {Sense cosuppression in plants: Past, present, and future},
booktitle = {RNAi: A guide to gene silencing},
publisher = {Cold Spring Harbor Laboratory Press},
year = {2003},
editor = {Hannon, G. J.},
address = {Cold Spring Harbor, NY},
keywords = {sirna},
owner = {vert},
timestamp = {2006.03.29}
}
@article{Kertesz2007role,
author = {Michael Kertesz and Nicola Iovino and Ulrich Unnerstall and Ulrike
Gaul and Eran Segal},
title = {The role of site accessibility in microRNA target recognition.},
journal = {Nat Genet},
year = {2007},
volume = {39},
pages = {1278--1284},
number = {10},
month = {Oct},
abstract = {MicroRNAs are key regulators of gene expression, but the precise mechanisms
underlying their interaction with their mRNA targets are still poorly
understood. Here, we systematically investigate the role of target-site
accessibility, as determined by base-pairing interactions within
the mRNA, in microRNA target recognition. We experimentally show
that mutations diminishing target accessibility substantially reduce
microRNA-mediated translational repression, with effects comparable
to those of mutations that disrupt sequence complementarity. We devise
a parameter-free model for microRNA-target interaction that computes
the difference between the free energy gained from the formation
of the microRNA-target duplex and the energetic cost of unpairing
the target to make it accessible to the microRNA. This model explains
the variability in our experiments, predicts validated targets more
accurately than existing algorithms, and shows that genomes accommodate
site accessibility by preferentially positioning targets in highly
accessible regions. Our study thus demonstrates that target accessibility
is a critical factor in microRNA function.},
doi = {10.1038/ng2135},
pdf = {../local/Kertesz2007role.pdf},
file = {Kertesz2007role.pdf:Kertesz2007role.pdf:PDF},
institution = {omputer Science and Applied Mathematics, Weizmann Institute of Science,
Rehovot 76100, Israel.},
keywords = {sirna},
language = {eng},
medline-pst = {ppublish},
owner = {jp},
pii = {ng2135},
pmid = {17893677},
timestamp = {2009.10.28},
url = {http://dx.doi.org/10.1038/ng2135}
}
@article{Khvorova2003Functional,
author = {Khvorova, A. and Reynolds, A. and Jayasena, S.D.},
title = {Functional si{RNA}s and mi{RNA}s exhibit strand bias.},
journal = {Cell},
year = {2003},
volume = {115},
pages = {209-216},
number = {2},
month = {Oct},
abstract = {Both micro{RNA}s (mi{RNA}) and small interfering {RNA}s (si{RNA})
share a common set of cellular proteins ({D}icer and the {RNA}-induced
silencing complex [{RISC}]) to elicit {RNA} interference. {I}n the
following work, a statistical analysis of the internal stability
of published mi{RNA} sequences in the context of mi{RNA} precursor
hairpins revealed enhanced flexibility of mi{RNA} precursors, especially
at the 5?-anti-sense ({AS}) terminal base pair. {T}he same trend
was observed in si{RNA}, with functional duplexes displaying a lower
internal stability (?0.5 kcal/mol) at the 5?-{AS} end than nonfunctional
duplexes. {A}verage internal stability of si{RNA} molecules retrieved
from plant cells after introduction of long {RNA} sequences also
shows this characteristic thermodynamic signature. {T}ogether, these
results suggest that the thermodynamic properties of si{RNA} play
a critical role in determining the molecule's function and longevity,
possibly biasing the steps involved in duplex unwinding and strand
retention by {RISC}.},
doi = {10.1016/S0092-8674(03)00801-8},
pdf = {../local/Khvorova2003Functional.pdf},
file = {Khvorova2003Functional.pdf:local/Khvorova2003Functional.pdf:PDF},
keywords = {sirna},
url = {http://dx.doi.org/10.1016/S0092-8674(03)00801-8}
}
@article{Lewis2005Conserved,
author = {Benjamin P Lewis and Christopher B Burge and David P Bartel},
title = {Conserved seed pairing, often flanked by adenosines, indicates that
thousands of human genes are microRNA targets.},
journal = {Cell},
year = {2005},
volume = {120},
pages = {15--20},
number = {1},
month = {Jan},
abstract = {We predict regulatory targets of vertebrate microRNAs (miRNAs) by
identifying mRNAs with conserved complementarity to the seed (nucleotides
2-7) of the miRNA. An overrepresentation of conserved adenosines
flanking the seed complementary sites in mRNAs indicates that primary
sequence determinants can supplement base pairing to specify miRNA
target recognition. In a four-genome analysis of 3' UTRs, approximately
13,000 regulatory relationships were detected above the estimate
of false-positive predictions, thereby implicating as miRNA targets
more than 5300 human genes, which represented 30\% of our gene set.
Targeting was also detected in open reading frames. In sum, well
over one third of human genes appear to be conserved miRNA targets.},
doi = {10.1016/j.cell.2004.12.035},
pdf = {../local/Lewis2005Conserved.pdf},
file = {Lewis2005Conserved.pdf:Lewis2005Conserved.pdf:PDF},
keywords = {sirna},
language = {eng},
medline-pst = {ppublish},
owner = {jp},
pii = {S0092867404012607},
pmid = {15652477},
timestamp = {2009.10.28},
url = {http://dx.doi.org/10.1016/j.cell.2004.12.035}
}
@article{Lewis2003Prediction,
author = {Benjamin P Lewis and I-hung Shih and Matthew W Jones-Rhoades and
David P Bartel and Christopher B Burge},
title = {Prediction of mammalian microRNA targets.},
journal = {Cell},
year = {2003},
volume = {115},
pages = {787--798},
number = {7},
month = {Dec},
abstract = {MicroRNAs (miRNAs) can play important gene regulatory roles in nematodes,
insects, and plants by basepairing to mRNAs to specify posttranscriptional
repression of these messages. However, the mRNAs regulated by vertebrate
miRNAs are all unknown. Here we predict more than 400 regulatory
target genes for the conserved vertebrate miRNAs by identifying mRNAs
with conserved pairing to the 5' region of the miRNA and evaluating
the number and quality of these complementary sites. Rigorous tests
using shuffled miRNA controls supported a majority of these predictions,
with the fraction of false positives estimated at 31\% for targets
identified in human, mouse, and rat and 22\% for targets identified
in pufferfish as well as mammals. Eleven predicted targets (out of
15 tested) were supported experimentally using a HeLa cell reporter
system. The predicted regulatory targets of mammalian miRNAs were
enriched for genes involved in transcriptional regulation but also
encompassed an unexpectedly broad range of other functions.},
institution = {Department of Biology, Massachusetts Institute of Technology, Cambridge,
MA 02139, USA.},
keywords = {sirna},
language = {eng},
medline-pst = {ppublish},
owner = {jp},
pii = {S0092867403010183},
pmid = {14697198},
timestamp = {2009.10.28}
}
@article{Lim2005Microarray,
author = {Lee P Lim and Nelson C Lau and Philip Garrett-Engele and Andrew Grimson
and Janell M Schelter and John Castle and David P Bartel and Peter
S Linsley and Jason M Johnson},
title = {Microarray analysis shows that some microRNAs downregulate large
numbers of target mRNAs.},
journal = {Nature},
year = {2005},
volume = {433},
pages = {769--773},
number = {7027},
month = {Feb},
abstract = {MicroRNAs (miRNAs) are a class of noncoding RNAs that post-transcriptionally
regulate gene expression in plants and animals. To investigate the
influence of miRNAs on transcript levels, we transfected miRNAs into
human cells and used microarrays to examine changes in the messenger
RNA profile. Here we show that delivering miR-124 causes the expression
profile to shift towards that of brain, the organ in which miR-124
is preferentially expressed, whereas delivering miR-1 shifts the
profile towards that of muscle, where miR-1 is preferentially expressed.
In each case, about 100 messages were downregulated after 12 h. The
3' untranslated regions of these messages had a significant propensity
to pair to the 5' region of the miRNA, as expected if many of these
messages are the direct targets of the miRNAs. Our results suggest
that metazoan miRNAs can reduce the levels of many of their target
transcripts, not just the amount of protein deriving from these transcripts.
Moreover, miR-1 and miR-124, and presumably other tissue-specific
miRNAs, seem to downregulate a far greater number of targets than
previously appreciated, thereby helping to define tissue-specific
gene expression in humans.},
doi = {10.1038/nature03315},
institution = {Rosetta Inpharmatics, Merck and Co, 401 Terry Avenue N, Seattle,
Washington 98109, USA. lee_lim@merck.com},
keywords = {sirna},
language = {eng},
medline-pst = {ppublish},
owner = {jp},
pii = {nature03315},
pmid = {15685193},
timestamp = {2009.10.28},
url = {http://dx.doi.org/10.1038/nature03315}
}
@article{Lytle2007Target,
author = {J. Robin Lytle and Therese A Yario and Joan A Steitz},
title = {Target mRNAs are repressed as efficiently by microRNA-binding sites
in the 5' UTR as in the 3' UTR.},
journal = {Proc Natl Acad Sci U S A},
year = {2007},
volume = {104},
pages = {9667--9672},
number = {23},
month = {Jun},
abstract = {In animals, microRNAs (miRNAs) bind to the 3' UTRs of their target
mRNAs and interfere with translation, although the exact mechanism
of inhibition of protein synthesis remains unclear. Functional miRNA-binding
sites in the coding regions or 5' UTRs of endogenous mRNAs have not
been identified. We studied the effect of introducing miRNA target
sites into the 5' UTR of luciferase reporter mRNAs containing internal
ribosome entry sites (IRESs), so that potential steric hindrance
by a microribonucleoprotein complex would not interfere with the
initiation of translation. In human HeLa cells, which express endogenous
let-7a miRNA, the translational efficiency of these IRES-containing
reporters with 5' let-7 complementary sites from the Caenorhabditis
elegans lin-41 3' UTR was repressed. Similarly, the IRES-containing
reporters were translationally repressed when human Ago2 was tethered
to either the 5' or 3' UTR. Interestingly, the method of DNA transfection
affected our ability to observe miRNA-mediated repression. Our results
suggest that association with any position on a target mRNA is mechanistically
sufficient for a microribonucleoprotein to exert repression of translation
at some step downstream of initiation.},
doi = {10.1073/pnas.0703820104},
institution = {Department of Molecular Biophysics and Biochemistry, Howard Hughes
Medical Institute, Yale University School of Medicine, New Haven,
CT 06536, USA.},
keywords = {sirna},
language = {eng},
medline-pst = {ppublish},
owner = {jp},
pii = {0703820104},
pmid = {17535905},
timestamp = {2009.10.28},
url = {http://dx.doi.org/10.1073/pnas.0703820104}
}
@article{Ma2004Structural,
author = {Ma, J.B. and Ye, K. and Patel, D.J.},
title = {{S}tructural basis for overhang-specific small interfering {RNA}
recognition by the {PAZ} domain.},
journal = {Nature},
year = {2004},
volume = {429},
pages = {318--322},
number = {6989},
month = {May},
abstract = {Short RNAs mediate gene silencing, a process associated with virus
resistance, developmental control and heterochromatin formation in
eukaryotes. RNA silencing is initiated through Dicer-mediated processing
of double-stranded RNA into small interfering RNA (siRNA). The siRNA
guide strand associates with the Argonaute protein in silencing effector
complexes, recognizes complementary sequences and targets them for
silencing. The PAZ domain is an RNA-binding module found in Argonaute
and some Dicer proteins and its structure has been determined in
the free state. Here, we report the 2.6 A crystal structure of the
PAZ domain from human Argonaute eIF2c1 bound to both ends of a 9-mer
siRNA-like duplex. In a sequence-independent manner, PAZ anchors
the 2-nucleotide 3' overhang of the siRNA-like duplex within a highly
conserved binding pocket, and secures the duplex by binding the 7-nucleotide
phosphodiester backbone of the overhang-containing strand and capping
the 5'-terminal residue of the complementary strand. On the basis
of the structure and on binding assays, we propose that PAZ might
serve as an siRNA-end-binding module for siRNA transfer in the RNA
silencing pathway, and as an anchoring site for the 3' end of guide
RNA within silencing effector complexes.},
doi = {10.1038/nature02519},
keywords = {sirna},
pii = {nature02519},
pmid = {15152257},
timestamp = {2006.07.08},
url = {http://dx.doi.org/10.1038/nature02519}
}
@article{Ma2005Structural,
author = {Ma, J-B. and Yuan, Y.-R. and Meister, G.. and Pei, Y. and Tuschl,
T. and Patel D.J.},
title = {Structural basis for 5'-end-specific recognition of guide {RNA} by
the {A}. fulgidus {PIWI} protein},
journal = {Nature},
year = {2005},
volume = {434},
pages = {666-670},
keywords = {sirna},
owner = {vert},
timestamp = {2006.04.27}
}
@article{Mathews1999Expanded,
author = {Mathews, D. H. and Sabina, J. and Zuker, M. and Turner, D. H.},
title = {Expanded sequence dependence of thermodynamic parameters improves
prediction of {RNA} secondary structure.},
journal = {J. {M}ol. {B}iol.},
year = {1999},
volume = {288},
pages = {911-40},
number = {5},
month = {May},
abstract = {An improved dynamic programming algorithm is reported for {RNA} secondary
structure prediction by free energy minimization. {T}hermodynamic
parameters for the stabilities of secondary structure motifs are
revised to include expanded sequence dependence as revealed by recent
experiments. {A}dditional algorithmic improvements include reduced
search time and storage for multibranch loop free energies and improved
imposition of folding constraints. {A}n extended database of 151,503
nt in 955 structures? determined by comparative sequence analysis
was assembled to allow optimization of parameters not based on experiments
and to test the accuracy of the algorithm. {O}n average, the predicted
lowest free energy structure contains 73 \% of known base-pairs when
domains of fewer than 700 nt are folded; this compares with 64 \%
accuracy for previous versions of the algorithm and parameters. {F}or
a given sequence, a set of 750 generated structures contains one
structure that, on average, has 86 \% of known base-pairs. {E}xperimental
constraints, derived from enzymatic and flavin mononucleotide cleavage,
improve the accuracy of structure predictions.},
doi = {10.1006/jmbi.1999.2700},
keywords = {sirna},
pii = {S0022-2836(99)92700-6},
url = {http://dx.doi.org/10.1006/jmbi.1999.2700}
}
@article{McManus2002Gene,
author = {McManus, M. T. and Sharp, P. A.},
title = {{G}ene silencing in mammals by small interfering {RNA}s.},
journal = {Nat. Rev. Genet.},
year = {2002},
volume = {3},
pages = {737--747},
number = {10},
month = {Oct},
abstract = {Among the 3 billion base pairs of the human genome, there are approximately
30,000-40,000 protein-coding genes, but the function of at least
half of them remains unknown. A new tool - short interfering RNAs
(siRNAs) - has now been developed for systematically deciphering
the functions and interactions of these thousands of genes. siRNAs
are an intermediate of RNA interference, the process by which double-stranded
RNA silences homologous genes. Although the use of siRNAs to silence
genes in vertebrate cells was only reported a year ago, the emerging
literature indicates that most vertebrate genes can be studied with
this technology.},
doi = {10.1038/nrg908},
pdf = {../local/McManus2002Gene.pdf},
file = {McManus2002Gene.pdf:McManus2002Gene.pdf:PDF},
keywords = {sirna},
owner = {vert},
pii = {nrg908},
pmid = {12360232},
timestamp = {2006.03.28},
url = {http://dx.doi.org/10.1038/nrg908}
}
@article{Meister2004Mechanisms,
author = {Meister, G. and Tuschl, T.},
title = {Mechanisms of gene silencing by double-stranded {RNA}.},
journal = {Nature},
year = {2004},
volume = {431},
pages = {343-9},
number = {7006},
month = {Sep},
abstract = {Double-stranded {RNA} (ds{RNA}) is an important regulator of gene
expression in many eukaryotes. {I}t triggers different types of gene
silencing that are collectively referred to as {RNA} silencing or
{RNA} interference. {A} key step in known silencing pathways is the
processing of ds{RNA}s into short {RNA} duplexes of characteristic
size and structure. {T}hese short ds{RNA}s guide {RNA} silencing
by specific and distinct mechanisms. {M}any components of the {RNA}
silencing machinery still need to be identified and characterized,
but a more complete understanding of the process is imminent.},
doi = {10.1038/nature02873},
pdf = {../local/Meister2004Mechanisms.pdf},
file = {Meister2004Mechanisms.pdf:local/Meister2004Mechanisms.pdf:PDF},
keywords = {sirna},
pii = {nature02873},
url = {http://dx.doi.org/10.1038/nature02873}
}
@article{Miranda2006pattern-based,
author = {Kevin C Miranda and Tien Huynh and Yvonne Tay and Yen-Sin Ang and
Wai-Leong Tam and Andrew M Thomson and Bing Lim and Isidore Rigoutsos},
title = {A pattern-based method for the identification of MicroRNA binding
sites and their corresponding heteroduplexes.},
journal = {Cell},
year = {2006},
volume = {126},
pages = {1203--1217},
number = {6},
month = {Sep},
abstract = {We present rna22, a method for identifying microRNA binding sites
and their corresponding heteroduplexes. Rna22 does not rely upon
cross-species conservation, is resilient to noise, and, unlike previous
methods, it first finds putative microRNA binding sites in the sequence
of interest, then identifies the targeting microRNA. Computationally,
we show that rna22 identifies most of the currently known heteroduplexes.
Experimentally, with luciferase assays, we demonstrate average repressions
of 30\% or more for 168 of 226 tested targets. The analysis suggests
that some microRNAs may have as many as a few thousand targets, and
that between 74\% and 92\% of the gene transcripts in four model
genomes are likely under microRNA control through their untranslated
and amino acid coding regions. We also extended the method's key
idea to a low-error microRNA-precursor-discovery scheme; our studies
suggest that the number of microRNA precursors in mammalian genomes
likely ranges in the tens of thousands.},
doi = {10.1016/j.cell.2006.07.031},
pdf = {../local/Miranda2006pattern-based.pdf},
file = {Miranda2006pattern-based.pdf:Miranda2006pattern-based.pdf:PDF},
institution = {Bioinformatics and Pattern Discovery Group, IBM Thomas J. Watson
Research Center, Yorktown Heights, P.O. Box 218, NY 10598, USA.},
keywords = {sirna},
language = {eng},
medline-pst = {ppublish},
owner = {jp},
pii = {S0092-8674(06)01099-3},
pmid = {16990141},
timestamp = {2009.10.28},
url = {http://dx.doi.org/10.1016/j.cell.2006.07.031}
}
@article{Mittal2004Improving,
author = {Mittal, V.},
title = {Improving the efficiency of {RNA} interference in mammals.},
journal = {Nat. {R}ev. {G}enet.},
year = {2004},
volume = {5},
pages = {355-65},
number = {5},
month = {May},
doi = {10.1038/nrg1323},
keywords = {sirna},
pii = {nrg1323},
url = {http://dx.doi.org/10.1038/nrg1323}
}
@article{Morin2008Application,
author = {Ryan D Morin and Michael D O'Connor and Malachi Griffith and Florian
Kuchenbauer and Allen Delaney and Anna-Liisa Prabhu and Yongjun Zhao
and Helen McDonald and Thomas Zeng and Martin Hirst and Connie J
Eaves and Marco A Marra},
title = {Application of massively parallel sequencing to microRNA profiling
and discovery in human embryonic stem cells.},
journal = {Genome Res},
year = {2008},
volume = {18},
pages = {610--621},
number = {4},
month = {Apr},
abstract = {MicroRNAs (miRNAs) are emerging as important, albeit poorly characterized,
regulators of biological processes. Key to further elucidation of
their roles is the generation of more complete lists of their numbers
and expression changes in different cell states. Here, we report
a new method for surveying the expression of small RNAs, including
microRNAs, using Illumina sequencing technology. We also present
a set of methods for annotating sequences deriving from known miRNAs,
identifying variability in mature miRNA sequences, and identifying
sequences belonging to previously unidentified miRNA genes. Application
of this approach to RNA from human embryonic stem cells obtained
before and after their differentiation into embryoid bodies revealed
the sequences and expression levels of 334 known plus 104 novel miRNA
genes. One hundred seventy-one known and 23 novel microRNA sequences
exhibited significant expression differences between these two developmental
states. Owing to the increased number of sequence reads, these libraries
represent the deepest miRNA sampling to date, spanning nearly six
orders of magnitude of expression. The predicted targets of those
miRNAs enriched in either sample shared common features. Included
among the high-ranked predicted gene targets are those implicated
in differentiation, cell cycle control, programmed cell death, and
transcriptional regulation.},
doi = {10.1101/gr.7179508},
pdf = {../local/Morin2008Application.pdf},
file = {Morin2008Application.pdf:Morin2008Application.pdf:PDF},
institution = {Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia
V5Z 1L3, Canada.},
keywords = {ngs, sirna},
language = {eng},
medline-pst = {ppublish},
owner = {jp},
pii = {gr.7179508},
pmid = {18285502},
timestamp = {2009.10.28},
url = {http://dx.doi.org/10.1101/gr.7179508}
}
@article{Overhoff2005Local,
author = {Overhoff, M. and Alken, M. and Far, R. K. and Lemaitre, M. and Lebleu,
B. and Sczakiel, G. and Robbins, I.},
title = {{L}ocal {RNA} target structure influences si{RNA} efficacy: a systematic
global analysis.},
journal = {J. Mol. Biol.},
year = {2005},
volume = {348},
pages = {871--881},
number = {4},
month = {May},
abstract = {The efficiency with which small interfering RNAs (siRNAs) down-regulate
specific gene expression in living cells is variable and a number
of sequence-governed, biochemical parameters of the siRNA duplex
have been proposed for the design of an efficient siRNA. Some of
these parameters have been clearly identified to influence the assembly
of the RNA-induced silencing complex (RISC), or to favour the sequence
preferences of the RISC endonuclease. For other parameters, it is
difficult to ascertain whether the influence is a determinant of
the siRNA per se, or a determinant of the target RNA, especially
its local structural characteristics. In order to gain an insight
into the effects of local target structure on the biological activity
of siRNA, we have used large sets of siRNAs directed against local
targets of the mRNAs of ICAM-1 and survivin. Target structures were
classified as accessible or inaccessible using an original, iterative
computational approach and by experimental RNase H mapping. The effectiveness
of siRNA was characterized by measuring the IC50 values in cell culture
and the maximal extent of target suppression. Mean IC50 values were
tenfold lower for accessible local target sites, with respect to
inaccessible ones. Mean maximal target suppression was improved.
These data illustrate that local target structure does, indeed, influence
the activity of siRNA. We suggest that local target screening can
significantly improve the hit rate in the design of biologically
active siRNAs.},
doi = {10.1016/j.jmb.2005.03.012},
keywords = {sirna},
owner = {vert},
pii = {S0022-2836(05)00270-6},
pmid = {15843019},
timestamp = {2006.03.28},
url = {http://dx.doi.org/10.1016/j.jmb.2005.03.012}
}
@article{Pai2006Prospects,
author = {Pai, S. I. and Lin, Y.-Y. and Macaes, B. and Meneshian, A. and HungC.-F.
and Wu, T.-C.},
title = {{P}rospects of {RNA} interference therapy for cancer.},
journal = {Gene Ther.},
year = {2006},
volume = {13},
pages = {464--477},
number = {6},
month = {Mar},
abstract = {RNA interference (RNAi) is a powerful gene-silencing process that
holds great promise in the field of cancer therapy. The discovery
of RNAi has generated enthusiasm within the scientific community,
not only because it has been used to rapidly identify key molecules
involved in many disease processes including cancer, but also because
RNAi has the potential to be translated into a technology with major
therapeutic applications. Our evolving understanding of the molecular
pathways important for carcinogenesis has created opportunities for
cancer therapy employing RNAi technology to target the key molecules
within these pathways. Many gene products involved in carcinogenesis
have already been explored as targets for RNAi intervention, and
RNAi targeting of molecules crucial for tumor-host interactions and
tumor resistance to chemo- or radiotherapy has also been investigated.
In most of these studies, the silencing of critical gene products
by RNAi technology has generated significant antiproliferative and/or
proapoptotic effects in cell-culture systems or in preclinical animal
models. Nevertheless, significant obstacles, such as in vivo delivery,
incomplete suppression of target genes, nonspecific immune responses
and the so-called off-target effects, need to be overcome before
this technology can be successfully translated into the clinical
arena. Significant progress has already been made in addressing some
of these issues, and it is foreseen that early phase clinical trials
will be initiated in the very near future.},
doi = {10.1038/sj.gt.3302694},
keywords = {sirna},
owner = {vert},
pii = {3302694},
pmid = {16341059},
timestamp = {2006.03.28},
url = {http://dx.doi.org/10.1038/sj.gt.3302694}
}
@article{Qiu2005computational,
author = {Qiu, S. and Adema, C. M. and Lane, T.},
title = {{A} computational study of off-target effects of {RNA} interference.},
journal = {Nucleic Acids Res.},
year = {2005},
volume = {33},
pages = {1834--1847},
number = {6},
abstract = {RNA interference (RNAi) is an intracellular mechanism for post-transcriptional
gene silencing that is frequently used to study gene function. RNAi
is initiated by short interfering RNA (siRNA) of approximately 21
nt in length, either generated from the double-stranded RNA (dsRNA)
by using the enzyme Dicer or introduced experimentally. Following
association with an RNAi silencing complex, siRNA targets mRNA transcripts
that have sequence identity for destruction. A phenotype resulting
from this knockdown of expression may inform about the function of
the targeted gene. However, 'off-target effects' compromise the specificity
of RNAi if sequence identity between siRNA and random mRNA transcripts
causes RNAi to knockdown expression of non-targeted genes. The complete
off-target effects must be investigated systematically on each gene
in a genome by adjusting a group of parameters, which is too expensive
to conduct experimentally and motivates a study in silico. This computational
study examined the potential for off-target effects of RNAi, employing
the genome and transcriptome sequence data of Homo sapiens, Caenorhabditis
elegans and Schizosaccharomyces pombe. The chance for RNAi off-target
effects proved considerable, ranging from 5 to 80\% for each of the
organisms, when using as parameter the exact identity between any
possible siRNA sequences (arbitrary length ranging from 17 to 28
nt) derived from a dsRNA (range 100-400 nt) representing the coding
sequences of target genes and all other siRNAs within the genome.
Remarkably, high-sequence specificity and low probability for off-target
reactivity were optimally balanced for siRNA of 21 nt, the length
observed mostly in vivo. The chance for off-target RNAi increased
(although not always significantly) with greater length of the initial
dsRNA sequence, inclusion into the analysis of available untranslated
region sequences and allowing for mismatches between siRNA and target
sequences. siRNA sequences from within 100 nt of the 5' termini of
coding sequences had low chances for off-target reactivity. This
may be owing to coding constraints for signal peptide-encoding regions
of genes relative to regions that encode for mature proteins. Off-target
distribution varied along the chromosomes of C.elegans, apparently
owing to the use of more unique sequences in gene-dense regions.
Finally, biological and thermodynamical descriptors of effective
siRNA reduced the number of potential siRNAs compared with those
identified by sequence identity alone, but off-target RNAi remained
likely, with an off-target error rate of approximately 10\%. These
results also suggest a direction for future in vivo studies that
could both help in calibrating true off-target rates in living organisms
and also in contributing evidence toward the debate of whether siRNA
efficacy is correlated with, or independent of, the target molecule.
In summary, off-target effects present a real but not prohibitive
concern that should be considered for RNAi experiments.},
doi = {10.1093/nar/gki324},
keywords = {sirna},
owner = {vert},
pii = {33/6/1834},
pmid = {15800213},
timestamp = {2006.04.27},
url = {http://dx.doi.org/10.1093/nar/gki324}
}
@article{Ren2006siRecords,
author = {Ren, Y. and Gong, W. and Xu, Q. and Zheng, X. and Lin, D. and Wang,
Y. and Li, T.},
title = {si{R}ecords: an extensive database of mammalian si{RNA}s with efficacy
ratings.},
journal = {Bioinformatics},
year = {2006},
month = {Jan},
abstract = {SUMMARY: Short interfering RNAs have been gaining popularity as the
gene knock-down tool of choice by many researchers due to the clean
nature of their workings as well as the technical simplicity and
cost efficiency in their applications. We have constructed siRecords,
a database of siRNAs experimentally tested by researchers with consistent
efficacy ratings. This database will help siRNA researchers develop
more reliable siRNA design rules; in the mean time, benefit experimental
researchers directly by providing them with information about the
siRNAs that have been experimentally tested against the genes of
their interest. Currently, more than 4, 100 carefully annotated siRNA
sequences obtained from more than 1, 200 published siRNA studies
are hosted in siRecords. This database will continue to expand as
more experimentally tested siRNAs are published. AVAILABILITY: The
siRecords database can be accessed at http://siRecords.umn.edu/siRecords/.},
doi = {10.1093/bioinformatics/btl026},
keywords = {sirna},
owner = {vert},
pii = {btl026},
pmid = {16443930},
timestamp = {2006.03.28},
url = {http://dx.doi.org/10.1093/bioinformatics/btl026}
}
@article{Reynolds2004Rational,
author = {Reynolds, A. and Leake, D. and Boese, Q. and Scaringe, S. and Marshall,
W. S. and Khvorova, A.},
title = {Rational si{RNA} design for {RNA} interference.},
journal = {Nat. {B}iotechnol.},
year = {2004},
volume = {22},
pages = {326-330},
number = {3},
month = {Mar},
abstract = {Short-interfering {RNA}s suppress gene expression through a highly
regulated enzyme-mediated process called {RNA} interference ({RNA}i)1,
2, 3, 4. {RNA}i involves multiple {RNA}-protein interactions characterized
by four major steps: assembly of si{RNA} with the {RNA}-induced silencing
complex ({RISC}), activation of the {RISC}, target recognition and
target cleavage. {T}hese interactions may bias strand selection during
si{RNA}-{RISC} assembly and activation, and contribute to the overall
efficiency of {RNA}i5, 6. {T}o identify si{RNA}-specific features
likely to contribute to efficient processing at each step, we performed
a systematic analysis of 180 si{RNA}s targeting the m{RNA} of two
genes. {E}ight characteristics associated with si{RNA} functionality
were identified: low {G}/{C} content, a bias towards low internal
stability at the sense strand 3'-terminus, lack of inverted repeats,
and sense strand base preferences (positions 3, 10, 13 and 19). {F}urther
analyses revealed that application of an algorithm incorporating
all eight criteria significantly improves potent si{RNA} selection.
{T}his highlights the utility of rational design for selecting potent
si{RNA}s and facilitating functional gene knockdown studies.},
doi = {10.1038/nbt936},
pdf = {../local/Reynolds2004Rational.pdf},
file = {Reynolds2004Rational.pdf:local/Reynolds2004Rational.pdf:PDF},
keywords = {sirna},
url = {http://dx.doi.org/10.1038/nbt936}
}
@article{Rhoades2002Prediction,
author = {Matthew W Rhoades and Brenda J Reinhart and Lee P Lim and Christopher
B Burge and Bonnie Bartel and David P Bartel},
title = {Prediction of plant microRNA targets.},
journal = {Cell},
year = {2002},
volume = {110},
pages = {513--520},
number = {4},
month = {Aug},
abstract = {We predict regulatory targets for 14 Arabidopsis microRNAs (miRNAs)
by identifying mRNAs with near complementarity. Complementary sites
within predicted targets are conserved in rice. Of the 49 predicted
targets, 34 are members of transcription factor gene families involved
in developmental patterning or cell differentiation. The near-perfect
complementarity between plant miRNAs and their targets suggests that
many plant miRNAs act similarly to small interfering RNAs and direct
mRNA cleavage. The targeting of developmental transcription factors
suggests that many plant miRNAs function during cellular differentiation
to clear key regulatory transcripts from daughter cell lineages.},
pdf = {../local/Rhoades2002Prediction.pdf},
file = {Rhoades2002Prediction.pdf:Rhoades2002Prediction.pdf:PDF},
institution = {Whitehead Institute for Biomedical Research, 9 Cambridge Center,
MA 02142, USA.},
keywords = {sirna},
language = {eng},
medline-pst = {ppublish},
owner = {jp},
pii = {S0092867402008632},
pmid = {12202040},
timestamp = {2009.10.28}
}
@article{Saetrom2004comparison,
author = {Saetrom, P. and Snøve, O.},
title = {A comparison of si{RNA} efficacy predictors.},
journal = {Biochem. {B}iophys. {R}es. {C}ommun.},
year = {2004},
volume = {321},
pages = {247-53},
number = {1},
month = {Aug},
abstract = {Short interfering {RNA} (si{RNA}) efficacy prediction algorithms aim
to increase the probability of selecting target sites that are applicable
for gene silencing by {RNA} interference. {M}any algorithms have
been published recently, and they base their predictions on such
different features as duplex stability, sequence characteristics,
m{RNA} secondary structure, and target site uniqueness. {W}e compare
the performance of the algorithms on a collection of publicly available
si{RNA}s. {F}irst, we show that our regularized genetic programming
algorithm {GP}boost appears to have a higher and more stable performance
than other algorithms on the collected datasets. {S}econd, several
algorithms gave close to random classification on unseen data, and
only {GP}boost and three other algorithms have a reasonably high
and stable performance on all parts of the dataset. {T}hird, the
results indicate that the si{RNA}s' sequence is sufficient input
to si{RNA} efficacy algorithms, and that other features that have
been suggested to be important may be indirectly captured by the
sequence.},
doi = {10.1016/j.bbrc.2004.06.116},
keywords = {sirna},
pii = {S0006-291X(04)01394-4},
url = {http://dx.doi.org/10.1016/j.bbrc.2004.06.116}
}
@article{Scacheri2004Short,
author = {Scacheri, P. C. and Rozenblatt-Rosen, O. and Caplen, N. J. and Wolfsberg,
T. G. and Umayam, L. and Lee, J. C. and Hughes, C. M. and Shanmugam,
K. S. and Bhattacharjee, A. and Meyerson, M. and Collins, F. S.},
title = {Short interfering {RNA}s can induce unexpected and divergent changes
in the levels of untargeted proteins in mammalian cells.},
journal = {Proc. {N}atl. {A}cad. {S}ci. {USA}},
year = {2004},
volume = {101},
pages = {1892-7},
number = {7},
month = {Feb},
abstract = {R{NA} interference ({RNA}i) mediated by short interfering {RNA}s (si{RNA}s)
is a widely used method to analyze gene function. {T}o use {RNA}i
knockdown accurately to infer gene function, it is essential to determine
the specificity of si{RNA}-mediated {RNA}i. {W}e have assessed the
specificity of 10 different si{RNA}s corresponding to the {MEN}1
gene by examining the expression of two additional genes, {TP}53
(p53) and {CDKN}1{A} (p21), which are considered functionally unrelated
to menin but are sensitive markers of cell state. {MEN}1 {RNA} and
corresponding protein levels were all reduced after si{RNA} transfection
of {H}e{L}a cells, although the degree of inhibition mediated by
individual si{RNA}s varied. {U}nexpectedly, we observed dramatic
and significant changes in protein levels of p53 and p21 that were
unrelated to silencing of the target gene. {T}he modulations in p53
and p21 levels were not abolished on titration of the si{RNA}s, and
similar results were obtained in three other cell lines; in none
of the cell lines tested did we see an effect on the protein levels
of actin. {T}hese data suggest that si{RNA}s can induce nonspecific
effects on protein levels that are si{RNA} sequence dependent but
that these effects may be difficult to detect until genes central
to a pivotal cellular response, such as p53 and p21, are studied.
{W}e find no evidence that activation of the double-stranded {RNA}-triggered
{IFN}-associated antiviral pathways accounts for these effects, but
we speculate that partial complementary sequence matches to off-target
genes may result in a micro-{RNA}-like inhibition of translation.},
doi = {10.1073/pnas.0308698100},
keywords = {sirna},
pii = {0308698100},
url = {http://dx.doi.org/10.1073/pnas.0308698100}
}
@article{Schubert2005Local,
author = {Schubert, S. and Grünweller, A. and Erdmann, V. A. and Kurreck,
J.},
title = {{L}ocal {RNA} target structure influences si{RNA} efficacy: systematic
analysis of intentionally designed binding regions.},
journal = {J. Mol. Biol.},
year = {2005},
volume = {348},
pages = {883--893},
number = {4},
month = {May},
abstract = {Contradictory reports in the literature have emphasised either the
sequence of small interfering RNAs (siRNA) or the structure of their
target molecules to be the major determinant of the efficiency of
RNA interference (RNAi) approaches. In the present study, we analyse
systematically the contributions of these parameters to siRNA activity
by using deliberately designed mRNA constructs. The siRNA target
sites were included in well-defined structural elements rendering
them either highly accessible or completely involved in stable base-pairing.
Furthermore, complementary sequence elements and various hairpins
with different stem lengths and designs were used as target sites.
Only one of the strands of the siRNA duplex was found to be capable
of silencing via its respective target site, indicating that thermodynamic
characteristics intrinsic to the siRNA strands are a basic determinant
of siRNA activity. A significant obstruction of gene silencing by
the same siRNA, however, was observed to be caused by structural
features of the substrate RNA. Bioinformatic analysis of the mRNA
structures suggests a direct correlation between the extent of gene-knockdown
and the local free energy in the target region. Our findings indicate
that, although a favourable siRNA sequence is a necessary prerequisite
for efficient RNAi, complex target structures may limit the applicability
even of carefully chosen siRNAs.},
doi = {10.1016/j.jmb.2005.03.011},
keywords = {sirna},
owner = {vert},
pii = {S0022-2836(05)00269-X},
pmid = {15843020},
timestamp = {2006.03.28},
url = {http://dx.doi.org/10.1016/j.jmb.2005.03.011}
}
@article{Schwarz2003Asymmetry,
author = {Schwarz, D. S. and Hutvagner, G. and Du, T. and Xu, Z. and Aronin,
N. and Zamore, P. D.},
title = {Asymmetry in the assembly of the {RNA}i enzyme complex},
journal = {Cell},
year = {2003},
volume = {115},
pages = {199-208},
number = {2},
month = {Oct},
abstract = {A key step in {RNA} interference ({RNA}i) is assembly of the {RISC},
the protein-si{RNA} complex that mediates target {RNA} cleavage.
{H}ere, we show that the two strands of an si{RNA} duplex are not
equally eligible for assembly into {RISC}. {R}ather, both the absolute
and relative stabilities of the base pairs at the 5? ends of the
two si{RNA} strands determine the degree to which each strand participates
in the {RNA}i pathway. si{RNA} duplexes can be functionally asymmetric,
with only one of the two strands able to trigger {RNA}i. {A}symmetry
is the hallmark of a related class of small, single-stranded, noncoding
{RNA}s, micro{RNA}s (mi{RNA}s). {W}e suggest that single-stranded
mi{RNA}s are initially generated as si{RNA}-like duplexes whose structures
predestine one strand to enter the {RISC} and the other strand to
be destroyed. {T}hus, the common step of {RISC} assembly is an unexpected
source of asymmetry for both si{RNA} function and mi{RNA} biogenesis.},
doi = {10.1016/S0092-8674(03)00759-1},
pdf = {../local/Schwarz2003Asymmetry.pdf},
file = {Schwarz2003Asymmetry.pdf:local/Schwarz2003Asymmetry.pdf:PDF},
keywords = {sirna},
url = {http://dx.doi.org/10.1016/S0092-8674(03)00759-1}
}
@article{Semizarov2003Specificity,
author = {Semizarov, D. and Frost, L. and Sarthy, A. and Kroeger, P. and Halbert,
D. N. and Fesik, S. W.},
title = {Specificity of short interfering {RNA} determined through gene expression
signatures.},
journal = {Proc. {N}atl. {A}cad. {S}ci. {USA}},
year = {2003},
volume = {100},
pages = {6347-52},
number = {11},
month = {May},
abstract = {Short interfering {RNA} (si{RNA}) is widely used for studying gene
function and holds great promise as a tool for validating drug targets
and treating disease. {A} critical assumption in these applications
is that the effect of si{RNA} on cells is specific, i.e., limited
to the specific knockdown of the target gene. {I}n this article,
we characterize the specificity of si{RNA} by applying gene expression
profiling. {S}everal si{RNA}s were designed against different regions
of the same target gene for three different targets. {T}heir effects
on cells were compared by using {DNA} microarrays to generate gene
expression signatures. {W}hen the si{RNA} design and transfection
conditions were optimized, the signatures for different si{RNA}s
against the same target were shown to correlate very closely, whereas
the signatures for different genes revealed no correlation. {T}hese
results indicate that si{RNA} is a highly specific tool for targeted
gene knockdown, establishing si{RNA}-mediated gene silencing as a
reliable approach for large-scale screening of gene function and
drug target validation.},
doi = {10.1073/pnas.1131959100},
keywords = {sirna},
pii = {1131959100},
url = {http://dx.doi.org/10.1073/pnas.1131959100}
}
@article{Shabalina2006Computational,
author = {Shabalina, S. and Spiridonov, A. and Ogurtsov, A.},
title = {{C}omputational models with thermodynamic and composition features
improve si{RNA} design.},
journal = {BMC Bioinformatics},
year = {2006},
volume = {7},
pages = {65},
number = {1},
month = {Feb},
abstract = {ABSTRACT: BACKGROUND: Small interfering RNAs (siRNAs) have become
an important tool in cell and molecular biology. Reliable design
of siRNA molecules is essential for the needs of large functional
genomics projects. RESULTS: To improve the design of efficient siRNA
molecules, we performed a comparative, thermodynamic and correlation
analysis on a heterogeneous set of 653 siRNAs collected from the
literature. We used this training set to select siRNA features and
optimize computational models. We identified 18 parameters that correlate
significantly with silencing efficiency. Some of these parameters
characterize only the siRNA sequence, while others involve the whole
mRNA. Most importantly, we derived an siRNA position-dependent consensus,
and optimized the free-energy difference of the 5' and 3' terminal
dinucleotides of the siRNA antisense strand. The position-dependent
consensus is based on correlation and t-test analyses of the training
set, and accounts for both significantly preferred and avoided nucleotides
in all sequence positions. On the training set, the two parameters'
correlation with silencing efficiency was 0.5 and 0.36, respectively.
Among other features, a dinucleotide content index and the frequency
of potential targets for siRNA in the mRNA added predictive power
to our model (R = 0.55). We showed that our model is effective for
predicting the efficiency of siRNAs at different concentrations.
We optimized a neural network model on our training set using three
parameters characterizing the siRNA sequence, and predicted efficiencies
for the test siRNA dataset recently published by Novartis. On this
validation set, the correlation coefficient between predicted and
observed efficiency was 0.75. Using the same model, we performed
a transcriptome-wide analysis of optimal siRNA targets for 22,600
human mRNAs. CONCLUSIONS: We demonstrated that the properties of
the siRNAs themselves are essential for efficient RNA interference.
The 5' ends of antisense strands of efficient siRNAs are U-rich and
possess a content similarity to the pyrimidine-rich oligonucleotides
interacting with the polypurine RNA tracks that are recognized by
RNase H. The advantage of our method over similar methods is the
small number of parameters. As a result, our method requires a much
smaller training set to produce consistent results. Other mRNA features,
though expensive to compute, can slightly improve our model.},
doi = {10.1186/1471-2105-7-65},
pdf = {../local/Shabalina2006Computational.pdf},
file = {Shabalina2006Computational.pdf:local/Shabalina2006Computational.pdf:PDF},
keywords = {sirna},
owner = {vert},
pii = {1471-2105-7-65},
pmid = {16472402},
timestamp = {2006.03.28},
url = {http://dx.doi.org/10.1186/1471-2105-7-65}
}
@article{Snoeve2004Designing,
author = {Snøve, O. and Nedland, M. and Fjeldstad, S. H. and Humberset, H.
and Birkeland, O. R. and Gr{\"o}nfeld, T. and Saetrom, P.},
title = {Designing effective si{RNA}s with off-target control.},
journal = {Biochem. {B}iophys. {R}es. {C}ommun.},
year = {2004},
volume = {325},
pages = {769-73},
number = {3},
month = {Dec},
abstract = {Successful gene silencing by {RNA} interference requires a potent
and specific depletion of the target m{RNA}. {T}arget candidates
must be chosen so that their corresponding short interfering {RNA}s
are likely to be effective against that target and unlikely to accidentally
silence other transcripts due to sequence similarity. {W}e show that
both effective and unique targets exist in mouse, fruit fly, and
worm, and present a new design tool that enables users to make the
trade-off between efficacy and uniqueness. {T}he tool lists all targets
with partial sequence similarity to the primary target to highlight
candidates for negative controls.},
doi = {10.1016/j.bbrc.2004.10.097},
keywords = {sirna},
pii = {S0006-291X(04)02391-5},
url = {http://dx.doi.org/10.1016/j.bbrc.2004.10.097}
}
@article{Surabhi2002RNA,
author = {Surabhi, R. M. and Gaynor, R. B.},
title = {{RNA} interference directed against viral and cellular targets inhibits
human immunodeficiency {V}irus {T}ype 1 replication.},
journal = {J. Virol.},
year = {2002},
volume = {76},
pages = {12963--12973},
number = {24},
month = {Dec},
abstract = {Human immunodeficiency virus type 1 (HIV-1) gene expression is regulated
by both cellular transcription factors and Tat. The ability of Tat
to stimulate transcriptional elongation is dependent on its binding
to TAR RNA in conjunction with cyclin T1 and CDK9. A variety of other
cellular factors that bind to the HIV-1 long terminal repeat, including
NF-kappaB, SP1, LBP, and LEF, are also important in the control of
HIV-1 gene expression. Although these factors have been demonstrated
to regulate HIV-1 gene expression by both genetic and biochemical
analysis, in most cases a direct in vivo demonstration of their role
on HIV-1 replication has not been established. Recently, the efficacy
of RNA interference in mammalian cells has been shown utilizing small
interfering RNAs (siRNAs) to result in the specific degradation of
host mRNAs and decreases the levels of their corresponding proteins.
In this study, we addressed whether siRNAs directed against either
HIV-1 tat or reverse transcriptase or the NF-kappaB p65 subunit could
specifically decrease the levels of these proteins and thus alter
HIV-1 replication. Our results demonstrate the specificity of siRNAs
for decreasing the expression of these viral and cellular proteins
and inhibiting HIV-1 replication. These studies suggest that RNA
interference is useful in exploring the biological role of cellular
and viral regulatory factors involved in the control of HIV-1 gene
expression.},
keywords = {sirna},
owner = {vert},
pmid = {12438622},
timestamp = {2006.03.28}
}
@article{Tang2005siRNA,
author = {Tang, G.},
title = {{siRNA} and {miRNA}: an insight into {RISC}s.},
journal = {Trends {B}iochem. {S}ci.},
year = {2005},
volume = {30},
pages = {106-14},
number = {2},
month = {Feb},
abstract = {Two classes of short {RNA} molecule, small interfering {RNA} (si{RNA})
and micro{RNA} (mi{RNA}), have been identified as sequence-specific
posttranscriptional regulators of gene expression. si{RNA} and mi{RNA}
are incorporated into related {RNA}-induced silencing complexes ({RISC}s),
termed si{RISC} and mi{RISC}, respectively. {T}he current model argues
that si{RISC} and mi{RISC} are functionally interchangeable and target
specific m{RNA}s for cleavage or translational repression, depending
on the extent of sequence complementarity between the small {RNA}
and its target. {E}merging evidence indicates, however, that si{RISC}
and mi{RISC} are distinct complexes that regulate m{RNA} stability
and translation. {T}he assembly of {RISC}s can be traced from the
biogenesis of the small {RNA} molecules and the recruitment of these
{RNA}s by the {RISC} loading complex ({RLC}) to the transition of
the {RLC} into the active {RISC}. {T}arget recognition by the {RISC}
can then take place through different interacting modes.},
doi = {10.1016/j.tibs.2004.12.007},
keywords = {sirna},
pii = {S0968-0004(04)00321-4},
url = {http://dx.doi.org/10.1016/j.tibs.2004.12.007}
}
@article{Teramoto2005Prediction,
author = {Reiji Teramoto and Mikio Aoki and Toru Kimura and Masaharu Kanaoka},
title = {Prediction of si{RNA} functionality using generalized string kernel
and support vector machine.},
journal = {F{EBS} {L}ett.},
year = {2005},
volume = {579},
pages = {2878-82},
number = {13},
month = {May},
abstract = {Small interfering {RNA}s (si{RNA}s) are becoming widely used for sequence-specific
gene silencing in mammalian cells, but designing an effective si{RNA}
is still a challenging task. {I}n this study, we developed an algorithm
for predicting si{RNA} functionality by using generalized string
kernel ({GSK}) combined with support vector machine ({SVM}). {W}ith
{GSK}, si{RNA} sequences were represented as vectors in a multi-dimensional
feature space according to the numbers of subsequences in each si{RNA},
and subsequently classified with {SVM} into effective or ineffective
si{RNA}s. {W}e applied this algorithm to published si{RNA}s, and
could classify effective and ineffective si{RNA}s with 90.6\%, 86.2\%
accuracy, respectively.},
doi = {10.1016/j.febslet.2005.04.045},
pdf = {../local/Teramoto2005Prediction.pdf},
file = {Teramoto2005Prediction.pdf:local/Teramoto2005Prediction.pdf:PDF},
keywords = {sirna biosvm},
pii = {S0014-5793(05)00520-X},
url = {http://dx.doi.org/10.1016/j.febslet.2005.04.045}
}
@article{Tomari2005Perspective,
author = {Tomari, Y. and Zamore, P. D.},
title = {Perspective: machines for {RNA}i.},
journal = {Genes {D}ev.},
year = {2005},
volume = {19},
pages = {517-29},
number = {5},
month = {Mar},
abstract = {R{NA} silencing pathways convert the sequence information in long
{RNA}, typically double-stranded {RNA}, into approximately 21-nt
{RNA} signaling molecules such as small interfering {RNA}s (si{RNA}s)
and micro{RNA}s (mi{RNA}s). si{RNA}s and mi{RNA}s provide specificity
to protein effector complexes that repress m{RNA} transcription or
translation, or catalyze m{RNA} destruction. {H}ere, we review our
current understanding of how small {RNA}s are produced, how they
are loaded into protein complexes, and how they repress gene expression.},
doi = {10.1101/gad.1284105},
keywords = {sirna},
pii = {19/5/517},
url = {http://dx.doi.org/10.1101/gad.1284105}
}
@article{Truss2005HuSiDa,
author = {Truss, M. and Swat, M. and Kielbasa, S. M. and Sch{\"a}fer, R. and
Herzel, H. and Hagemeier, C.},
title = {Hu{S}i{D}a--the human si{RNA} database: an open-access database for
published functional si{RNA} sequences and technical details of efficient
transfer into recipient cells.},
journal = {Nucleic {A}cids {R}es.},
year = {2005},
volume = {33},
pages = {D108-11},
number = {Database issue},
month = {Jan},
abstract = {Small interfering {RNA}s (si{RNA}s) have become a standard tool in
functional genomics. {O}nce incorporated into the {RNA}-induced silencing
complex ({RISC}), si{RNA}s mediate the specific recognition of corresponding
target m{RNA}s and their cleavage. {H}owever, only a small fraction
of randomly chosen si{RNA} sequences is able to induce efficient
gene silencing. {I}n common laboratory practice, successful {RNA}
interference experiments typically require both, the labour and cost-intensive
identification of an active si{RNA} sequence and the optimization
of target cell line-specific procedures for optimal si{RNA} delivery.
{T}o optimize the design and performance of si{RNA} experiments,
we have established the human si{RNA} database ({H}u{S}i{D}a). {T}he
database provides sequences of published functional si{RNA} molecules
targeting human genes and important technical details of the corresponding
gene silencing experiments, including the mode of si{RNA} generation,
recipient cell lines, transfection reagents and procedures and direct
links to published references ({P}ub{M}ed). {T}he database can be
accessed at http://www.human-si{RNA}-database.net. {W}e used the
si{RNA} sequence information stored in the database for scrutinizing
published sequence selection parameters for efficient gene silencing.},
doi = {10.1093/nar/gki131},
keywords = {sirna},
pii = {33/suppl_1/D108},
url = {http://dx.doi.org/10.1093/nar/gki131}
}
@article{Ui-Tei2004Guidelines,
author = {Ui-Tei, K. and Naito, Y. and Takahashi, F. and Haraguchi, T. and
Ohki-Hamazaki, H. and Juni, A. and Ueda, R. and Saigo, K.},
title = {Guidelines for the selection of highly effective si{RNA} sequences
for mammalian and chick {RNA} interference.},
journal = {Nucleic {A}cids {R}es.},
year = {2004},
volume = {32},
pages = {936-948},
number = {3},
month = {Feb},
abstract = {In the present study, the relationship between short interfering {RNA}
(si{RNA}) sequence and {RNA} interference ({RNA}i) effect was extensively
analyzed using 62 targets of four exogenous and two endogenous genes
and three mammalian and {D}rosophila cells. {W}e present the rules
that may govern si{RNA} sequence preference and in accordance with
which highly effective si{RNA}s essential for systematic mammalian
functional genomics can be readily designed. {T}hese rules indicate
that si{RNA}s which simultaneously satisfy all four of the following
sequence conditions are capable of inducing highly effective gene
silencing in mammalian cells: (i) {A}/{U} at the 5' end of the antisense
strand; (ii) {G}/{C} at the 5' end of the sense strand; (iii) at
least five {A}/{U} residues in the 5' terminal one-third of the antisense
strand; and (iv) the absence of any {GC} stretch of more than 9 nt
in length. si{RNA}s opposite in features with respect to the first
three conditions give rise to little or no gene silencing in mammalian
cells. {E}ssentially the same rules for si{RNA} sequence preference
were found applicable to {DNA}-based {RNA}i in mammalian cells and
in ovo {RNA}i using chick embryos. {I}n contrast to mammalian and
chick cells, little si{RNA} sequence preference could be detected
in {D}rosophila in vivo {RNA}i.},
doi = {10.1093/nar/gkh247},
keywords = {sirna},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/32/3/936}
}
@article{Vasudevan2007Switching,
author = {Shobha Vasudevan and Yingchun Tong and Joan A Steitz},
title = {Switching from repression to activation: microRNAs can up-regulate
translation.},
journal = {Science},
year = {2007},
volume = {318},
pages = {1931--1934},
number = {5858},
month = {Dec},
abstract = {AU-rich elements (AREs) and microRNA target sites are conserved sequences
in messenger RNA (mRNA) 3' untranslated regions (3'UTRs) that control
gene expression posttranscriptionally. Upon cell cycle arrest, the
ARE in tumor necrosis factor-alpha (TNFalpha) mRNA is transformed
into a translation activation signal, recruiting Argonaute (AGO)
and fragile X mental retardation-related protein 1 (FXR1), factors
associated with micro-ribonucleoproteins (microRNPs). We show that
human microRNA miR369-3 directs association of these proteins with
the AREs to activate translation. Furthermore, we document that two
well-studied microRNAs-Let-7 and the synthetic microRNA miRcxcr4-likewise
induce translation up-regulation of target mRNAs on cell cycle arrest,
yet they repress translation in proliferating cells. Thus, activation
is a common function of microRNPs on cell cycle arrest. We propose
that translation regulation by microRNPs oscillates between repression
and activation during the cell cycle.},
doi = {10.1126/science.1149460},
institution = {Department of Molecular Biophysics and Biochemistry, Howard Hughes
Medical Institute, Yale University School of Medicine, Boyer Center
for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06536,
USA.},
keywords = {sirna},
language = {eng},
medline-pst = {ppublish},
owner = {jp},
pii = {1149460},
pmid = {18048652},
timestamp = {2009.10.28},
url = {http://dx.doi.org/10.1126/science.1149460}
}
@article{Yamada2005Accelerated,
author = {Yamada, T. and Morishita, S.},
title = {Accelerated off-target search algorithm for si{RNA}.},
journal = {Bioinformatics},
year = {2005},
volume = {21},
pages = {1316-24},
number = {8},
month = {Apr},
abstract = {M{OTIVATION}: {D}esigning highly effective short interfering {RNA}
(si{RNA}) sequences with maximum target-specificity for mammalian
{RNA} interference ({RNA}i) is one of the hottest topics in molecular
biology. {T}he relationship between si{RNA} sequences and {RNA}i
activity has been studied extensively to establish rules for selecting
highly effective sequences. {H}owever, there is a pressing need to
compute si{RNA} sequences that minimize off-target silencing effects
efficiently and to match any non-targeted sequences with mismatches.
{RESULTS}: {T}he enumeration of potential cross-hybridization candidates
is non-trivial, because si{RNA} sequences are short, ca. 19 nt in
length, and at least three mismatches with non-targets are required.
{W}ith at least three mismatches, there are typically four or five
contiguous matches, so that a {BLAST} search frequently overlooks
off-target candidates. {B}y contrast, existing accurate approaches
are expensive to execute; thus we need to develop an accurate, efficient
algorithm that uses seed hashing, the pigeonhole principle, and combinatorics
to identify mismatch patterns. {T}ests show that our method can list
potential cross-hybridization candidates for any si{RNA} sequence
of selected human gene rapidly, outperforming traditional methods
by orders of magnitude in terms of computational performance. {AVAILABILITY}:
http://design.{RNA}i.jp {CONTACT}: yamada@cb.k.u-tokyo.ac.jp.},
doi = {10.1093/bioinformatics/bti155},
keywords = {sirna},
pii = {bti155},
url = {http://dx.doi.org/10.1093/bioinformatics/bti155}
}
@article{Zamore2000RNAi,
author = {Zamore, P.D. and Tuschl, T. and Sharp, P.A. and Bartel, D.P.},
title = {R{NA}i: double-stranded {RNA} directs the {ATP}-dependent cleavage
of m{RNA} at 21 to 23 nucleotide intervals.},
journal = {Cell},
year = {2000},
volume = {101},
pages = {25-33},
number = {1},
month = {Mar},
abstract = {Double-stranded {RNA} (ds{RNA}) directs the sequence-specific degradation
of m{RNA} through a process known as {RNA} interference ({RNA}i).
{U}sing a recently developed {D}rosophila in vitro system, we examined
the molecular mechanism underlying {RNA}i. {W}e find that {RNA}i
is {ATP} dependent yet uncoupled from m{RNA} translation. {D}uring
the {RNA}i reaction, both strands of the ds{RNA} are processed to
{RNA} segments 21-23 nucleotides in length. {P}rocessing of the ds{RNA}
to the small {RNA} fragments does not require the targeted m{RNA}.
{T}he m{RNA} is cleaved only within the region of identity with the
ds{RNA}. {C}leavage occurs at sites 21-23 nucleotides apart, the
same interval observed for the ds{RNA} itself, suggesting that the
21-23 nucleotide fragments from the ds{RNA} are guiding m{RNA} cleavage.},
doi = {10.1016/S0092-8674(00)80620-0},
keywords = {sirna},
pii = {S0092-8674(00)80620-0},
url = {http://dx.doi.org/10.1016/S0092-8674(00)80620-0}
}
@article{Zuker1989finding,
author = {Zuker, M.},
title = {{O}n finding all suboptimal foldings of an {RNA} molecule.},
journal = {Science},
year = {1989},
volume = {244},
pages = {48--52},
number = {4900},
month = {Apr},
abstract = {An algorithm and a computer program have been prepared for determining
RNA secondary structures within any prescribed increment of the computed
global minimum free energy. The mathematical problem of determining
how well defined a minimum energy folding is can now be solved. All
predicted base pairs that can participate in suboptimal structures
may be displayed and analyzed graphically. Representative suboptimal
foldings are generated by selecting these base pairs one at a time
and computing the best foldings that contain them. A distance criterion
that ensures that no two structures are "too close" is used to avoid
multiple generation of similar structures. Thermodynamic parameters,
including free-energy increments for single-base stacking at the
ends of helices and for terminal mismatched pairs in interior and
hairpin loops, are incorporated into the underlying folding model
of the above algorithm.},
keywords = {sirna},
owner = {vert},
pmid = {2468181},
timestamp = {2006.04.27}
}
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omput. Biol.;J. Biol. Chem.;J. Biomed. Inform.;J. Cell. Biochem.;J. Ch
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st.;J. Mach. Learn. Res.;J. Med. Chem.;J. Mol. BIol.;J. R. Stat. Soc.
Ser. B;Journal of Statistical Planning and Inference;Mach. Learn.;Math
. Program.;Meth. Enzymol.;Mol. Biol. Cell;Mol. Biol. Evol.;Mol. Cell.
Biol.;Mol. Syst. Biol.;N. Engl. J. Med.;Nat. Biotechnol.;Nat. Genet.;N
at. Med.;Nat. Methods;Nat. Rev. Cancer;Nat. Rev. Drug Discov.;Nat. Rev
. Genet.;Nature;Neural Comput.;Neural Network.;Neurocomputing;Nucleic
Acids Res.;Pattern Anal. Appl.;Pattern Recognit.;Phys. Rev. E;Phys. Re
v. Lett.;PLoS Biology;PLoS Comput. Biol.;Probab. Theory Relat. Fields;
Proc. IEEE;Proc. Natl. Acad. Sci. USA;Protein Eng.;Protein Eng. Des. S
el.;Protein Sci.;Protein. Struct. Funct. Genet.;Random Struct. Algorit
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