RNA interference
NaturePublished 1 July 2002
Gregory J. Hannon
Citations3,499
SJR quartileQ1
SJR score18.29
SNIP10.16
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Abstract
A conserved biological response to double-stranded RNA, known variously as RNA interference (RNAi) or post-transcriptional gene silencing, mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes. RNAi has been cultivated as a means to manipulate gene expression experimentally and to probe gene function on a whole-genome scale.
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
NaturePotent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans
15,295 Citations1998Andrew Fire, Siqun Xu +4 more
To their surprise, it was found that double-stranded RNA was substantially more effective at producing interference than was either strand individually, arguing against stochiometric interference with endogenous mRNA and suggesting that there could be a catalytic or amplification component in the interference process.
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
9,370 Citations2001Sayda M. Elbashir, Jens Harborth +4 more
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NatureThe 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans
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Let-7 is shown to be a heterochronic switch gene that encodes a temporally regulated 21-nucleotide RNA that is complementary to elements in the 3′ untranslated regions of the heterochronic genes lin-14, lin-28, lin-41, lin-42 and daf-12, indicating that expression of these genes may be directly controlled by let-7.
ScienceIdentification of Novel Genes Coding for Small Expressed RNAs
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It is shown that many 21- and 22-nt expressed RNAs, termed microRNAs, exist in invertebrates and vertebrates and that some of these novel RNAs are highly conserved, which suggests that sequence-specific, posttranscriptional regulatory mechanisms mediated by smallRNAs are more general than previously appreciated.
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4,881 Citations2001Emily Bernstein, Amy A. Caudy +2 more
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.
CellPosttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans
4,240 Citations1993Bruce Wightman, Ilho Ha +1 more
It is demonstrated that a temporal gradient in Lin-14 protein is generated posttranscriptionally by multiple elements in the lin-14 3'UTR that are regulated by the heterochronic gene Lin-4.
ScienceAn Abundant Class of Tiny RNAs with Probable Regulatory Roles in <i>Caenorhabditis elegans</i>
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Two small temporal RNAs, lin-4 andlet-7, control developmental timing in Caenorhabditis elegans and are found to be members of a large class of 21- to 24-nucleotide noncodingRNAs, called microRNAs (miRNAs), which imply that, as a class, miRNAs have broad regulatory functions in animals.
ScienceA Species of Small Antisense RNA in Posttranscriptional Gene Silencing in Plants
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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.
NatureAn RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells
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ScienceAn Extensive Class of Small RNAs in <i>Caenorhabditis elegans</i>
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Using bioinformatics and cDNA cloning, this work found 15 new miRNA genes in C. elegans that express small transcripts that vary in abundance during larval development, and three of them have apparent homologs in mammals and/or insects.
ScienceA Cellular Function for the RNA-Interference Enzyme Dicer in the Maturation of the <i>let-7</i> Small Temporal RNA
2,650 Citations2001György Hutvágner, Juanita McLachlan +4 more
In Drosophila melanogaster a developmentally regulated precursor RNA is cleaved by an RNA interference-like mechanism to produce mature let-7 stRNA, which regulates developmental timing in Caenorhabditis elegans and probably in other bilateral animals.
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.
CellGenes and Mechanisms Related to RNA Interference Regulate Expression of the Small Temporal RNAs that Control C. elegans Developmental Timing
1,873 Citations2001Alla Grishok, Amy E. Pasquinelli +8 more
It is shown that inactivation of genes related to RNAi pathway genes, a homolog of Drosophila Dicer (dcr-1), and two homologs of rde-1 (alg-1 and alg-2), cause heterochronic phenotypes similar to lin-4 and let-7 mutations.
Genes & DevelopmentDicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in <i>C. elegans</i>
1,792 Citations2001René F. Ketting, Sylvia E. J. Fischer +4 more
Genes & DevelopmentShort hairpin RNAs (shRNAs) induce sequence-specific silencing in mammalian cells
1,555 Citations2002Patrick J. Paddison, Amy A. Caudy +3 more
Short hairpin RNAs (shRNAs) can be engineered to suppress the expression of desired genes in cultured Drosophila and mammalian cells and can be synthesized exogenously or transcribed from RNA polymerase III promoters in vivo, thus permitting the construction of continuous cell lines or transgenic animals in which RNAi enforces stable and heritable gene silencing.
ScienceArgonaute2, a Link Between Genetic and Biochemical Analyses of RNAi
1,518 Citations2001Scott M. Hammond, Sabrina Boettcher +3 more
Biochemical purification of the RNAi effector nuclease from cultured Drosophila cells reveals that one constituent of this complex is a member of the Argonaute family of proteins, which are essential for gene silencing in Caenorhabditis elegans, Neurospora, and Arabidopsis.
Nature GeneticsMicro RNAs are complementary to 3′ UTR sequence motifs that mediate negative post-transcriptional regulation
1,478 Citations2002Eric C. Lai
A large subset of Drosophila microRNAs is shown to be perfectly complementary to several classes of sequence motif previously demonstrated to mediate negative post-transcriptional regulation, suggesting a more general role for micro RNAs in gene regulation through the formation of RNA duplexes.
The EMBO JournalFunctional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate
1,451 Citations2001Sayda M. Elbashir, Javier Martinez +3 more
Duplexes of 21–23 nucleotide RNAs are the sequence‐specific mediators of RNA interference and post‐transcriptional gene silencing and mismatches in the centre of the siRNA duplex prevent target RNA cleavage, providing a rational basis for the design of siRNAs in future gene targeting experiments.
CellThe rde-1 Gene, RNA Interference, and Transposon Silencing in C. elegans
1,308 Citations1999Hiroaki Tabara, Madathia Sarkissian +6 more
It is shown that rde-1 is a member of the piwi/sting/argonaute/zwille/eIF2C gene family conserved from plants to vertebrates and the possibility that one natural function of RNAi is transposon silencing is discussed.
CellOn the Role of RNA Amplification in dsRNA-Triggered Gene Silencing
1,298 Citations2001Titia Sijen, Jamie Fleenor +6 more
Analysis of small interfering RNAs produced during RNAi in C. elegans revealed a substantial fraction that cannot derive directly from input dsRNA, and appeared to derive from the action of a cellular RNA-directed RNA polymerase (RdRP) on mRNAs that are being targeted by the RNAi mechanism.
Developmental BiologyThe lin-4 Regulatory RNA Controls Developmental Timing in Caenorhabditis elegans by Blocking LIN-14 Protein Synthesis after the Initiation of Translation
1,163 Citations1999Philip Olsen, Victor Ambros
The results indicate that association of lin-4 RNA with the 3' UTR of Lin-14 mRNA permits normal biogenesis of lin -14 mRNA, and normal translational initiation, but inhibits step(s) thereafter, such as translational elongation and/or the release of stable LIN-14 protein.
CellUse of dsRNA-Mediated Genetic Interference to Demonstrate that frizzled and frizzled 2 Act in the Wingless Pathway
1,120 Citations1998Jason R. Kennerdell, Richard W. Carthew
Investigation of the potential of double-stranded RNA to interfere with the function of genes in Drosophila demonstrated that dsRNA interference can be used to analyze many aspects of gene function.
Cellpar-1, a gene required for establishing polarity in C. elegans embryos, encodes a putative Ser/Thr kinase that is asymmetrically distributed
1,115 Citations1995Su Guo, Kenneth J. Kemphues
It is reported here that par-1 encodes a putative Ser/Thr kinase with similarity to kinases from yeasts and mammals, suggesting that kinase activity is essential for par-2 function and in establishing embryonic polarity.
Proceedings of the National Academy of SciencesA DNA vector-based RNAi technology to suppress gene expression in mammalian cells
1,111 Citations2002Guangchao Sui, Christina Soohoo +5 more
This work reports a technology that allows synthesis of small interfering RNAs from DNA templates in vivo to efficiently inhibit endogenous gene expression and demonstrates robust inhibition of several endogenous genes of diverse functions in mammalian cells.
CellArabidopsis SGS2 and SGS3 Genes Are Required for Posttranscriptional Gene Silencing and Natural Virus Resistance
1,090 Citations2000Philippe Mourrain, Christophe Béclin +12 more
Both sgs2 and sgs3 mutants show enhanced susceptibility to virus, definitively proving that PTGS is an antiviral defense mechanism that can also target transgene RNA for degradation.
Genes & DevelopmentmiRNPs: a novel class of ribonucleoproteins containing numerous microRNAs
1,070 Citations2002Zissimos P. Mourelatos, Josée Dostie +7 more
This work reports that Gemin3 and Gemin4 are also in a separate complex that contains eIF2C2, a member of the Argonaute protein family, which is a large approximately 15S RNP that contains numerous microRNAs (miRNAs).
CellAn RNA-Dependent RNA Polymerase Gene in Arabidopsis Is Required for Posttranscriptional Gene Silencing Mediated by a Transgene but Not by a Virus
1,064 Citations2000Tamás Dalmay, Andrew J. Hamilton +3 more
It is proposed that the role of SDE1 is to synthesize a double-stranded RNA initiator of posttranscriptional gene silencing, according to this idea, when a virus induces posttranscriptal genesilencing, the virus-encoded RNA polymerase would produce the double-Stranded RNA and Sde1 would be redundant.
CellATP Requirements and Small Interfering RNA Structure in the RNA Interference Pathway
1,002 Citations2001Antti Nykänen, Benjamin Haley +1 more
It is suggested that the RNAi reaction comprises at least four sequential steps: ATP-dependent processing of double-stranded RNA into small interfering RNAs (siRNAs), incorporation of siRNAs into an inactive approximately 360 kDa protein/RNA complex, ATP- dependent unwinding of the siRNA duplex to generate an active complex, and ATP-independent recognition and cleavage of the RNA target.
The Plant CellInitiation and Maintenance of Virus-Induced Gene Silencing
993 Citations1998María Teresa Gil Ruiz, Olivier Voinnet +1 more
A model of virus-induced gene silencing (VIGS) is proposed in which the initiation of VIGS is dependent on the virus and maintenance of it is virus independent, and the VIGs of the GFP was targeted against PVX–GFP.
Genes & DevelopmentA novel class of evolutionarily conserved genes defined by <i>piwi</i> are essential for stem cell self-renewal
982 Citations1998Daniel N. Cox, Anna Chao +4 more
The Drosophila piwi gene is cloned and characterized and it is shown that it is required for the asymmetric division of GSCs to produce and maintain a daughter GSC but is not essential for the further differentiation of the committed daughter cell.
NatureTotal silencing by intron-spliced hairpin RNAs
957 Citations2000Neil A. Smith, Surinder Singh +4 more
It is shown that gene constructs encoding intron-spliced RNA with a hairpin structure can induce post-transcriptional gene silencing with almost 100% efficiency when directed against viruses or endogenous genes.
CellRNA-directed de novo methylation of genomic sequences in plants
926 Citations1994Michael Wassenegger, Sabine Heimes +2 more
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.
ScienceSystemic RNAi in <i>C. elegans</i> Requires the Putative Transmembrane Protein SID-1
863 Citations2002William M. Winston, Christina Molodowitch +1 more
This strain was constructed to identify systemic RNA interference–deficient (sid) loci required to spread gene-silencing information between tissues but not to initiate or maintain an RNAi response, and encodes a conserved protein with predicted transmembrane domains.
ScienceA Role for the RNase III Enzyme DCR-1 in RNA Interference and Germ Line Development in <i>Caenorhabditis elegans</i>
862 Citations2001Scott W. Knight, Brenda Bass
A null mutation indicer-1 (dcr-1), a gene proposed to encode the enzyme that generates short RNAs, is described and it is found that Mutant animals have defects in RNAi under some, but not all, conditions.
The EMBO JournalTranscriptional silencing and promoter methylation triggered by double‐stranded RNA
859 Citations2000Michael Florian Mette, Werner Aufsatz +3 more
It is shown here that transcriptional gene silencing accompanied by de novo methylation of a target promoter in plants can be triggered by a double‐stranded RNA containing promoter sequences.
Nature Reviews GeneticsPost-transcriptional gene silencing by double-stranded RNA
848 Citations2001Scott M. Hammond, Amy A. Caudy +1 more
The power of RNA interference, the process by which double-stranded RNA induces the silencing of homologous endogenous genes, is slowly becoming clear, and might help to develop an effortless tool to probe gene function in cells and animals.
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.
Molecular MicrobiologyQuelling: transient inactivation of gene expression in <i>Neurospora crassa</i> by transformation with homologous sequences
815 Citations1992Nicoletta Romano, Giuseppe Macino
The phenotypic reversion is characterized by a progressive release of the transcriptional inhibition and seems to correlate with a reduction of the number of the ectopic integrated sequences, which indicates that quelling appears to be monodirectional, as, once relieved, it cannot take place again, despite the continuing presence of some of theectopic sequences in the genome.
The EMBO JournalSystemic acquired silencing: transgene‐specific post‐transcriptional silencing is transmitted by grafting from silenced stocks to non‐silenced scions
777 Citations1997J. C. Palauqui, Taline Elmayan +2 more
Results suggest that a non‐metabolic, transgene‐specific, diffusable messenger mediates the propagation of de novo post‐transcriptional silencing through the plant.
Molecular CellThe lin-41 RBCC Gene Acts in the C. elegans Heterochronic Pathway between the let-7 Regulatory RNA and the LIN-29 Transcription Factor
757 Citations2000Frank J. Slack, Michael Basson +4 more
It is suggested that late larval activation of let-7 RNA expression downregulates LIN-41 to relieve inhibition of lin-29, and this work concludes that the C. elegans heterochronic gene lin-41 negatively regulates the timing of LIN-29 adult specification transcription factor expression.
Cellmut-7 of C. elegans, Required for Transposon Silencing and RNA Interference, Is a Homolog of Werner Syndrome Helicase and RNaseD
746 Citations1999René F. Ketting, Thomas Haverkamp +2 more
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.
Nature Cell BiologySpecific interference with gene function by double-stranded RNA in early mouse development
722 Citations1999Florence Wianny, Magdalena Zernicka‐Goetz
It is shown that dsRNA is effective as a specific inhibitor of the function of three genes in the mouse, namely maternally expressed c-mos in the oocyte and zygotically expressed E-cadherin or a GFP transgene in the preimplantation embryo.
Proceedings of the National Academy of SciencesCytoplasmic inhibition of carotenoid biosynthesis with virus-derived RNA.
714 Citations1995Monto H. Kumagai, Jonathan Donson +4 more
This work demonstrates that an episomal RNA viral vector can be used to deliberately manipulate a major, eukaryotic biosynthetic pathway and indicates that an antisense transcript generated in the cytoplasm of a plant cell can turn off endogenous gene expression.
CellSystemic Spread of Sequence-Specific Transgene RNA Degradation in Plants Is Initiated by Localized Introduction of Ectopic Promoterless DNA
696 Citations1998Olivier Voinnet, Philippe Vain +2 more
Systemic, posttranscriptional silencing of transgenes in Nicotiana benthamiana was initiated in localized regions of the plant by introduction of transgene-homologous DNA fragments, including those without a promoter.
The EMBO JournalAGO1 defines a novel locus of Arabidopsis controlling leaf development
678 Citations1998Karen Bohmert, Isabelle Camus +4 more
An allelic series of the novel argonaute mutant (ago1‐1 to ago1‐6) of the herbaceous plant Arabidopsis thaliana has been isolated and encodes a putative 115 kDa protein with sequence similarity to translation products of a novel gene family present in nematodes as well as humans.
CellA Viral Movement Protein Prevents Spread of the Gene Silencing Signal in Nicotiana benthamiana
671 Citations2000Olivier Voinnet, Carsten W. Lederer +1 more
It is demonstrated with potato virus X (PVX) that PTGS operates as a systemic, sequence-specific defense system, but in grafting experiments or with movement defective forms of PVX, it could not detect systemic silencing unless the 25 kDa viral movement protein (p25) was made nonfunctional.
NatureGene silencing in Neurospora crassa requires a protein homologous to RNA-dependent RNA polymerase
659 Citations1999Carlo Cogoni, Giuseppe Macino
The cloning of qde-1, the first cellular component of the gene-silencing mechanism to be isolated, defines a new gene family conserved among different species including plants, animals and fungi, which is similar to an RNA-dependent RNA polymerase found in the tomato.
The Plant CellFertile Hypomorphic <i>ARGONAUTE</i> (<i>ago1</i>) Mutants Impaired in Post-Transcriptional Gene Silencing and Virus Resistance
624 Citations2002Jean‐Benoît Morel, Christian Godon +6 more
Proceedings of the National Academy of SciencesAGO1, QDE-2, and RDE-1 are related proteins required for post-transcriptional gene silencing in plants, quelling in fungi, and RNA interference in animals
561 Citations2000Mathilde Fagard, Stéphanie Boutet +3 more
The isolation of Arabidopsis mutants impaired in PTGS and Sequencing of ago1 mutants revealed one amino acid essential for PTGS that is also present in QDE-2 and RDE-1 in a highly conserved motif confirm the hypothesis that these processes derive from a common ancestral mechanism that controls expression of invading nucleic acid molecules at the post-transcriptional level.
Proceedings of the National Academy of SciencesStable suppression of gene expression by RNAi in mammalian cells
550 Citations2002Patrick J. Paddison, Amy A. Caudy +1 more
It is shown that some cultured murine cells specifically silence gene expression upon treatment with long dsRNAs (≈500 nt), and this response shows hallmarks of conventional RNAi including silencing at the posttranscriptional level and the endogenous production of ≈22-nt small RNAs.
Current BiologyEGO-1 is related to RNA-directed RNA polymerase and functions in germ-line development and RNA interference in C. elegans
548 Citations2000Anne M. Smardon, Jill M. Spoerke +4 more
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532 Citations2000Zefeng Wang, James C. Morris +2 more
A vector for in vivo tetracycline-inducible synthesis of double-stranded RNA (dsRNA) in stably transformed cells is described and one striking phenotype was the loss of kinetoplast DNA after interference with expression of a topoisomerase II.
ScienceDNA Methylation and Epigenetic Inheritance in Plants and Filamentous Fungi
520 Citations2001Robert A. Martienssen, Vincent Colot
This work considers the role that transposons play in establishing methylation patterns and the epigenetic consequences of their perturbation in plants and filamentous fungi.
Nature BiotechnologyHeritable gene silencing in Drosophila using double-stranded RNA
512 Citations2000Jason R. Kennerdell, Richard W. Carthew
RNAi can be adapted to study late-acting gene function in Drosophila and is reported that the stably inherited transgene confers specific interference of gene expression in embryos, and tissues that give rise to adult structures such as the wings, legs, eyes, and brain.
ScienceGenetic Requirements for Inheritance of RNAi in <i>C. elegans</i>
458 Citations2000Alla Grishok, Hiroaki Tabara +1 more
Findings provide evidence for germ line transmission of an extragenic sequence-specific silencing factor and implicate rde-1 and r de-4 in the formation of the inherited agent.
The Plant CellSpreading of RNA Targeting and DNA Methylation in RNA Silencing Requires Transcription of the Target Gene and a Putative RNA-Dependent RNA Polymerase
445 Citations2002Fabián E. Vaistij, Louise Jones +1 more
It is shown that virus vectors carrying parts of a green fluorescent protein (GFP) transgene targeted RNA silencing in Nicotiana benthamiana and Arabidopsis against the entire GFP RNA, indicating that SDE1/SGS2 produces double-stranded RNA using the target RNA as a template.
Nature GeneticsHeritable and inducible genetic interference by double-stranded RNA encoded by transgenes
429 Citations2000Nektarios Tavernarakis, Shi L. Wang +3 more
This work assayed the efficacy of in vivo-driven RNAi in three situations for which heritable, inducible RNAi would be advantageous: production of large numbers of animals deficient for gene activities required for viability or reproduction; generation of large populations of phenocopy mutants for biochemical analysis; and effective gene inactivation in the nervous system.
DevelopmentSelective reduction of dormant maternal mRNAs in mouse oocytes by RNA interference
413 Citations2000Petr Svoboda, Paula Stein +2 more
In mouse oocytes, RNAi provides a suitable and robust approach to study the function of dormant maternal mRNAs and faithfully phenocopies the Mos null mutant.
Plant Molecular BiologyChalcone synthase cosuppression phenotypes in petunia flowers: comparison of sense vs. antisense constructs and single-copy vs. complex T-DNA sequences
383 Citations1996Richard A. Jorgensen, P. D. Cluster +3 more
The degree ofcosuppression observed in progeny of transgenotes carrying multiple, dispersed copies as compared to that observed with a single copy of the transgene suggests that sense cosuppression ofChs is subject to a transgenes dosage effect.
Molecular CellRNAi Related Mechanisms Affect Both Transcriptional and Posttranscriptional Transgene Silencing in Drosophila
377 Citations2002Manika Pal‐Bhadra, Utpal Bhadra +1 more
Two types of transgene silencing were found for the Alcohol dehydrogenase (Adh) transcription unit, and mutations in piwi, which belongs to a gene family with members required for RNAi, block PTGS and one aspect of TGS, indicating a connection between the two types of silencing.
The EMBO JournalRole of the ZWILLE gene in the regulation of central shoot meristem cell fate during Arabidopsis embryogenesis
377 Citations1998Bernard Moussian, Heiko Schoof +3 more
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CellRNAi as Random Degradative PCR
373 Citations2001Concetta Lipardi, Wei Qin +1 more
It is shown that GFP and Pp-Luc siRNAs, isolated from a protein complex in Drosophila embryo extract, target mRNA degradation in vitro and serve as primers to transform the target mRNA into dsRNA.
APOPTOSISInduction of apoptosis by the dsRNA-dependent protein kinase (PKR): Mechanism of action
371 Citations2000Jesús Gil, Mariano Estéban
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Current BiologyRNA-directed transcriptional gene silencing in plants can be inherited independently of the RNA trigger and requires Met1 for maintenance
363 Citations2001Louise Jones, Frank Ratcliff +1 more
Investigation of RNA-triggered events can lead to heritable changes in gene expression, and it is possible that initiation of other epigenetic phenomena such as trans-silencing and paramutation may have an RNA component.
DevelopmentDisruption of an RNA helicase/RNAse III gene in <i>Arabidopsis</i> causes unregulated cell division in floral meristems
363 Citations1999Steven E. Jacobsen, Mark Running +1 more
The CAF gene was cloned and found to encode a putative protein of 1909 amino acids containing an N-terminal DExH/DEAD-box type RNA helicase domain attached to a C-terminals RNaseIII-like domain, which may act through some type of RNA processing event(s).
The EMBO JournalSuppression of beta‐1,3‐glucanase transgene expression in homozygous plants.
304 Citations1992Fernanda de Carvalho‐Niebel, Godelieve Gheysen +4 more
By generating haploid plants, it is found that this silencing phenomenon is not dependent on allelic interaction between T‐DNA copies present at the same locus of homologous chromosomes, but rather is correlated with the transgene dose in the plant genome.
The Plant CellHC-Pro Suppression of Transgene Silencing Eliminates the Small RNAs but Not Transgene Methylation or the Mobile Signal
303 Citations2001Allison C. Mallory, Lara Ely +8 more
It is reported that plants in which PTGS has been suppressed by HC-Pro fail to accumulate the small RNAs associated with silencing, however, the transgene locus of these plants remains methylated.
The Plant JournalExpression of single copies of a strongly expressed <i>35S</i> transgene can be silenced post‐transcriptionally
294 Citations1996Taline T. Elmayan, Hervé Vaucheret
Trends in biotechnologyAltered gene expression in plants due totrans interactions between homologous genes
288 Citations1990Richard A. Jorgensen
It is speculated that there might be mechanistic similarities between co-suppression and some other trans interaction and epigenetic phenomena in plants, fungi and animals; and that it might be the sequence context in which a gene lies, or its location in the genome that influences the likelihood that it will participate in these phenomena.
ScienceTransgene and Transposon Silencing in <i>Chlamydomonas reinhardtii</i> by a DEAH-Box RNA Helicase
280 Citations2000Dancia Wu‐Scharf, Byeong‐ryool Jeong +2 more
A gene (Mut6) from the unicellular green alga Chlamydomonas reinhardtii is cloned that is required for the silencing of a transgene and two transposon families and encodes a protein that is highly homologous to RNA helicases of the DEAH-box family.
The Plant CellIsolation of an RNA-Directed RNA Polymerase–Specific cDNA Clone from Tomato
254 Citations1998Winfried Schiebel, Thierry Pélissier +7 more
Antibodies that were raised against synthetic peptides whose sequences have been deduced from the ORF were shown to specifically detect the 127-kD tomato RdRP protein.
DevelopmentProduction of antisense RNA leads to effective and specific inhibition of gene expression in <i>C. elegans</i> muscle
252 Citations1991Andrew Fire, Donna G. Albertson +2 more
Data suggest that the observed phenotypes result from interference with a late step in gene expression, such as transport into the cytoplasm or translation.
SciencePosttranscriptional Gene Silencing in <i>Neurospora</i> by a RecQ DNA Helicase
251 Citations1999Carlo Cogoni, Giuseppe Macino
The qde-3 gene, which is required for the activation and maintenance of gene silencing in the fungus Neurospora crassa, was isolated and sequence analysis revealed that it belongs to the RecQ DNA helicase family.
The EMBO JournalConsistent gene silencing in transgenic plants expressing a replicating potato virus X RNA
241 Citations1997Susan Angell, David C. Baulcombe
It is concluded that the replicating viral RNA is a potent trigger of gene Silencing in transgenic plants and amplicon‐mediated gene silencing provides an important new strategy for the consistent activation of genesilencing intransgenic plants.
CellCosuppression in Drosophila: Gene Silencing of Alcohol dehydrogenase by white-Adh Transgenes Is Polycomb Dependent
241 Citations1997Manika Pal‐Bhadra, Utpal Bhadra +1 more
When two to six copies of a white promoter-Alcohol dehydrogenase (Adh) reporter fusion gene are introduced into the genome, the expression is progressively reduced both in larvae and adults rather than the expected gene dosage effect.
StructureCrystallographic and Modeling Studies of RNase III Suggest a Mechanism for Double-Stranded RNA Cleavage
238 Citations2001Jarosław Błaszczyk, Joseph E. Tropea +5 more
A hypothetical model of Aa-RNase III in complex with dsRNA and Mg(2+) ion is constructed, which provides the first glimpse of RNaseIII in action and reveals a novel protein fold and suggest a mechanism for ds RNA cleavage.
Genes & DevelopmentA bulged lin-4/lin-14 RNA duplex is sufficient for Caenorhabditis elegans lin-14 temporal gradient formation.
233 Citations1996Ilho Ha, Bruce Wightman +1 more
Molecular and genetic evidence is reported that RNA duplexes between the lin-4 and lin-14 RNAs form in vivo and are necessary for LIN-14 temporal gradient generation, and suggests that a specific secondary structure of lin- 4/lin-14 RNA Duplex that may be recognized by an accessory protein, rather than anRNA duplex per se, is required in vivo for the generation of the LIN- 14 temporal gradient.
The Plant CellThe Frequency and Degree of Cosuppression by Sense Chalcone Synthase Transgenes Are Dependent on Transgene Promoter Strength and Are Reduced by Premature Nonsense Codons in the Transgene Coding Sequence.
198 Citations1997Qiudeng Que, H. Y. Wang +2 more
It is shown that a strong transgene promoter is required for high-frequency cosuppression of Chs genes and for production of the full range ofcosuppression phenotypes, and it is suggested that promoter strength and transcript stability determine the degree ofCosuppression.
RNAGenetic interference in Trypanosoma brucei by heritable and inducible double-stranded RNA
197 Citations2000Huafang Shi, Appolinaire Djikeng +4 more
It is shown that genetic interference by dsRNA can be achieved in a heritable and inducible fashion in Trypanosoma brucei and these new developments make it possible to initiate the molecular dissection of RNAi both biochemically and genetically.
Molecular Plant-Microbe InteractionsRNA-Mediated Virus Resistance in Transgenic Plants: Exploitation of a Cellular Pathway Possibly Involved in RNA Degradation
190 Citations1994William G. Dougherty
The highly resistant and recovery phenotypes associated with TEV challenge inoculation and the reduction of steady-state RNA levels in recovered transgenic leaf tissue may be manifestations of a common mechanism.
Genes & DevelopmentInvolvement of small RNAs and role of the <i>qde</i> genes in the gene silencing pathway in <i>Neurospora</i>
175 Citations2002Caterina Catalanotto, Gianluca Azzalin +2 more
It is found that small sense and antisense RNAs are also involved in PTGS in Neurospora crassa, suggesting that QDE2 could be part of a small RNA-directed ribonuclease complex involved in sequence-specific mRNA degradation.
Molecular and Biochemical ParasitologyDouble-stranded RNA interference in Trypanosoma brucei using head-to-head promoters
174 Citations2000Douglas LaCount, Shannon Bruse +2 more
The two-promoter approach efficiently generates dsRNAi in T. brucei and should be useful in generating knockout phenotypes in other kinetoplastid parasites including Trypanosoma cruzi and Leishmania.
Plant Molecular BiologyInhibition of flower pigmentation by antisense CHS genes: promoter and minimal sequence requirements for the antisense effect
159 Citations1990Alexander R. van der Krol, Leon A. Mur +3 more
It is concluded that the constitutive antisense CHS genes are not likely to provide an excess of antisense RNA compared to the CHS mRNA derived from the endogenous genes.
Genes & DevelopmentTransgene-mediated cosuppression in the <i>C. elegans</i> germ line
157 Citations2000Abby F. Dernburg, Jonathan Zalevsky +2 more
The generality of and definition of rules for a transgene-mediated cosuppression phenomenon in the Caenorhabditis elegans germ line are demonstrated and it is shown thatcosuppression and RNAi have overlapping but distinct genetic requirements.
ScienceRNA Helicase MUT-14-Dependent Gene Silencing Triggered in <i>C. elegans</i> by Short Antisense RNAs
150 Citations2002Marcel Tijsterman, René F. Ketting +3 more
It is shown that single-stranded RNA oligomers of antisense polarity can also be potent inducers of gene silencing, and the data favor the hypothesis that genesilencing is accomplished by RNA primer extension using the mRNA as template, leading to dsRNA that is subsequently degraded.
ScienceA Link Between RNA Interference and Nonsense-Mediated Decay in <i>Caenorhabditis elegans</i>
146 Citations2000Mary Ellen Domeier, Daniel P. Morse +4 more
It is suggested that persistence of RNA interference relies on a subset of smg genes, which are required for nonsense-mediated decay in animals that were initially silenced by dsRNA but then recovered; wild-type animals remained silenced.
GeneA novel type of RNase III family proteins in eukaryotes
139 Citations2000Valery Filippov, Victor Solovyev +2 more
A comparison of these drosha proteins to other members of the RNase III family indicates that they form a new group of proteins within this family.
GeneticsGene Silencing and Homology-Dependent Gene Silencing in Arabidopsis: Genetic Modifiers and DNA Methylation
126 Citations1998Ian J. Furner, Mazhar Sheikh +1 more
Two monogenic recessive trans-acting mutations that impair gene silencing and HDG silencing were identified and a further mutant (Catt) was isolated and has an attenuated HDG-silencing T-DNA, implying that DNA methylation is necessary for both gene silence and HDg silencing.
Proceedings of the National Academy of SciencesUsing RNA interference to identify genes required for RNA interference
125 Citations2002Nathaniel R. Dudley, Jean‐Claude Labbé +1 more
The finding that genes predicted to encode proteins that associate with chromatin are involved in RNAi in C. elegans raises the possibility that chromatin may play a role inRNAi in animals, as it does in plants.
Genes to CellsDevelopmental roles and molecular characterization of a <i>Drosophila</i> homologue of <i>Arabidopsis Argonaute1</i>, the founder of a novel gene superfamily
122 Citations2001Youhei Kataoka, Masatoshi Takeichi +1 more
Arabidopsis Argonaute1 (AGO1) is the founder of a novel gene superfamily that is conserved from fission yeasts to humans and is necessary for stem cell renewal or RNA interference.
Human Gene TherapyControl of the Functional Activity of an Antisense RNA by a Tetracycline-Responsive Derivative of the Human U6 snRNA Promoter
82 Citations2000Jun Ohkawa, Kazunari Taira
The results suggest that this expression system might be a useful tool for controlling the expression of functionalRNAs, such as aptamers and antisense RNAs, both in basic research and in gene therapy.
Nucleic Acids ResearchDevelopment of an inducible pol III transcription system essentially requiring a mutated form of the TATA-binding protein
11 Citations2001Wassilios G. Meissner
A transcription system in which a particular DNA sequence of interest could be inducibly expressed under the control of a modified polymerase III (pol III) promoter by fusing elements of the beta-lactamase gene of Escherichia coli to the initiation region of the human U6 gene.
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