The RNAi revolution
NaturePublished 1 July 2004
Carl D. Novina, Phillip A. Sharp
Citations723
SJR quartileQ1
SJR score18.29
SNIP10.16
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TL;DR
The term RNAi — short for RNA interference — crops up again and again in biology research these days because of its power as a laboratory tool, and in part because it is a widespread natural phenomenon.
Abstract
The term RNAi — short for RNA interference — crops up again and again in biology research these days. This is in part because of its power as a laboratory tool, and in part because it is a widespread natural phenomenon.
Keywords
Biochemistry, Genetics and Molecular Biology
NaturePotent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans
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CellThe C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14
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NatureDuplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells
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CellPrediction of Mammalian MicroRNA Targets
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NatureThe 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans
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NatureRole for a bidentate ribonuclease in the initiation step of RNA interference
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Dicer is a member of the RNase III family of nucleases that specifically cleave double-stranded RNAs, and is evolutionarily conserved in worms, flies, plants, fungi and mammals, and has a distinctive structure, which includes a helicase domain and dualRNase III motifs.
Genes & DevelopmentRNA interference is mediated by 21- and 22-nucleotide RNAs
3,306 Citations2001Sayda M. Elbashir, Winfried Lendeckel +1 more
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ScienceA Species of Small Antisense RNA in Posttranscriptional Gene Silencing in Plants
3,029 Citations1999Andrew J. Hamilton, David C. Baulcombe
The 25-nucleotide antisense RNA detected in transgene-induced PTGS is likely synthesized from an RNA template and may represent the specificity determinant of PTGS.
The Plant CellIntroduction of a Chimeric Chalcone Synthase Gene into Petunia Results in Reversible Co-Suppression of Homologous Genes in trans.
2,431 Citations1990Carolyn A. Napoli, Christine Lemieux +1 more
Somatic reversion of plants with white flowers to phenotypically parental violet flowers was associated with a coordinate rise in the steady-state levels of the mRNAs produced by both the endogenous and the introduced CHS genes, indicating that expression of the introduced chalcone synthase gene was not alone sufficient for suppression of endogenous CHS transcript levels.
Nucleic Acids ResearchThe microRNA Registry
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The miRNA Registry provides a service for the assignment of miRNA gene names prior to publication and a comprehensive and searchable database of published miRNA sequences is accessible via a web interface.
ScienceMicroRNA-Directed Cleavage of <i>HOXB8</i> mRNA
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Results point to a miRNA-mediated mechanism for the posttranscriptional restriction of HOX gene expression during vertebrate development and demonstrate that metazoan miRNAs can repress expression of their natural targets through mRNA cleavage in addition to inhibiting productive translation.
PLoS BiologyGenetic and Functional Diversification of Small RNA Pathways in Plants
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Molecular Biology of the CellRemodeling of Yeast Genome Expression in Response to Environmental Changes
1,389 Citations2001Helen C. Causton, Bing Ren +8 more
The results of expression analysis with MSN2/MSN4 mutants support the model that the Msn2/Msn4 activators induce the common response to environmental change and extend the understanding of the role of activators in effecting this response.
CellThe rde-1 Gene, RNA Interference, and Transposon Silencing in C. elegans
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Genes & DevelopmentsiRNAs can function as miRNAs
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It is shown that a short interfering RNA (siRNA) can repress expression of a target mRNA with partially complementary binding sites in its 3' UTR, much like the demonstrated function of endogenously encoded microRNAs (miRNAs).
ScienceRNAi-Mediated Targeting of Heterochromatin by the RITS Complex
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The purification of an RNAi effector complex termed RITS (RNA-induced initiation of transcriptional gene silencing) that is required for heterochromatin assembly in fission yeast is described and a mechanism for the role of the RNAi machinery and small RNAs in targeting of heterochROMatin complexes and epigenetic genesilencing at specific chromosomal loci is suggested.
Genes & DevelopmentThe microRNAs of <i>Caenorhabditis elegans</i>
1,232 Citations2003Lee P. Lim, Nelson C. Lau +6 more
The census of the worm miRNAs and their expression patterns helps define this class of noncoding RNAs, lays the groundwork for functional studies, and provides the tools for more comprehensive analyses of miRNA genes in other species.
ScienceVertebrate MicroRNA Genes
1,214 Citations2003Lee P. Lim, Margaret E. Glasner +3 more
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The Plant CellFlavonoid genes in petunia: addition of a limited number of gene copies may lead to a suppression of gene expression.
1,199 Citations1990Alexander R. van der Krol, Luis A. J. Mur +3 more
The similarity between the sense transformants and regulatory CHS mutants suggests that this mechanism of gene silencing may operate in naturally occurring regulatory circuits.
CellRNA-directed de novo methylation of genomic sequences in plants
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These findings demonstrate that a mechanism of de novo methylation of genes might exist that can be induced and targeted in a sequence-specific manner by their own mRNA.
Genes & DevelopmentTargeted mRNA degradation by double-stranded RNA in vitro
834 Citations1999Thomas Tuschl, Phillip D. Zamore +3 more
The development of a cell-free system from syncytial blastoderm Drosophila embryos that recapitulates many of the features of RNAi is reported, demonstrating that RNAi can be mediated by sequence-specific processes in soluble reactions.
Cellmut-7 of C. elegans, Required for Transposon Silencing and RNA Interference, Is a Homolog of Werner Syndrome Helicase and RNaseD
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This work mutagenized one silenced strain of C. elegans and isolated mutants in which Tc1 had been activated in the germline, finding one of the mutated genes, mut-7, to encode a protein with homology to RNaseD, providing support for the notion that RNAi works by dsRNA-directed, enzymatic RNA degradation.
Current BiologyMicroRNAs and Other Tiny Endogenous RNAs in C. elegans
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The presence of diverse endogenous siRNAs in normal worms suggests ongoing, genome-wide gene silencing by RNAi, and suggests that diverse modes of small RNA-mediated gene regulation are deployed innormal worms.
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It is demonstrated that this silencing is dependent on the RNA interference machinery, using tandem mini-white arrays and white transgenes in heterochromatin to show loss of silencing as a result of mutations in piwi, aubergine, or spindle-E (homeless), which encode RNAi components.
CellAnalysis of a piwi-Related Gene Implicates Small RNAs in Genome Rearrangement in Tetrahymena
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This work identified a gene, TWI1, in Tetrahymena thermophila that is homologous to piwi and is required for DNA elimination and found that small RNAs were specifically expressed prior to chromosome rearrangement during conjugation, and proposed that these smallRNAs function to specify sequences to be eliminated by a mechanism similar to RNA-mediated gene silencing.
CellA Small Modulatory dsRNA Specifies the Fate of Adult Neural Stem Cells
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Biochimica et Biophysica Acta (BBA) - Gene Structure and ExpressionGenetic analysis of RNA-mediated transcriptional gene silencing
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Results obtained so far indicate that in response to RNA signals, different site-specific DNA methyltransferases (DMTases) cooperate with each other and eventually with histone-modifying enzymes to establish and maintain a transcriptionally inactive state at a homologous target promoter.