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RNA interference: from an ancient mechanism to a state of the art therapeutic application?

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Abstract

Now that the sequencing of many genomes has been completed, the basic challenges are finding the genes and predicting their functions. Up until now, a large information gap has existed between the knowledge of genome sequence and our knowledge of protein function. The assessment of gene function may be performed using the tools of reverse genetics, including knock-out mice, antisense oligomers, aptamers, and ribozymes. These approaches have been superseded by RNA interference (RNAi), which exhibits much more potency for the investigation of protein function than the techniques listed above. As already known some years ago, RNAi is based on an ancient anti-viral defense mechanism in lower eukaryotes. It is induced by double-stranded RNA and its processing to 21–23 nt small interfering RNAs (siRNAs), which cause the degradation of homologous endogenous mRNA. The way RNAi works has still to be determined, but it already serves as a first-choice approach to generate loss-of-function phenotypes among a broad variety of eukaryotic species, such as nematodes, flies, plants, fungi and mammals. RNAi also represents an extremely powerful tool, becoming a therapeutic approach to curing infectious diseases originated by viral or parasitic invasion. In this review we present the current view of how RNAi works in different eukaryotic species and its high potential for functional genomics and in rational drug design.

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References

  • Anandalakshmi R, Marathe R, Ge X, Herr JM Jr, Mau C, Mallory A, Pruss G, Bowman L, Vance VB (2000) A calmodulin-related protein that suppresses posttranscriptional gene silencing in plants. Science 290:142–144

    Article  CAS  PubMed  Google Scholar 

  • Angell SM, Baulcombe DC (1997) Consistent gene silencing in transgenic plants expressing a replicating potato virus X RNA. EMBO J 16:3675–3684

    Article  CAS  PubMed  Google Scholar 

  • Angell SM, Baulcombe DC (1999) Potato virus X amplicon-mediated silencing of nuclear genes. Plant J 20:357–362

    Article  CAS  PubMed  Google Scholar 

  • Aravind L, Koonin EV (2001) A natural classification of ribonucleases. Methods Enzymol 341:3–28

    CAS  PubMed  Google Scholar 

  • Baulcombe DC (1999) Gene silencing: RNA makes RNA makes no protein. Curr Biol 9:R599–R601

    Article  CAS  PubMed  Google Scholar 

  • Beclin C, Boutet S, Waterhouse P, Vaucheret H (2002) A branched pathway for transgene-induced RNA silencing in plants. Curr Biol 12:684–688

    Article  CAS  PubMed  Google Scholar 

  • Bernstein E, Caudy AA, Hammond SM, Hannon GJ (2001) Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 409:363–366

    CAS  PubMed  Google Scholar 

  • Billy E, Brondani V, Zhang H, Muller U, Filipowicz W (2001) Specific interference with gene expression induced by long, double-stranded RNA in mouse embryonal teratocarcinoma cell lines. Proc Natl Acad Sci USA 98:14428–14433

    Article  CAS  PubMed  Google Scholar 

  • Blaszczyk J, Tropea JE, Bubunenko M, Routzahn KM, Waugh DS, Court DL, Ji XH (2001) Crystallographic and modeling studies of RNase III suggest a mechanism for double-stranded RNA cleavage. Structure 9:1225–1236

    Article  CAS  PubMed  Google Scholar 

  • Braasch DA, Corey DR (2002) Novel antisense and peptide nucleic acid strategies for controlling gene expression. Biochemistry 41:4503–4510

    Article  CAS  PubMed  Google Scholar 

  • Brantl S (2002) Antisense-RNA regulation and RNA interference. Biochim Biophys Acta 1575:15–25

    Article  CAS  PubMed  Google Scholar 

  • Brigneti G, Voinnet O, Li WX, Ji LH, Ding SW, Baulcombe DC (1998) Viral pathogenicity determinants are suppressors of transgene silencing in Nicotiana benthamiana. EMBO J 17:6739–6746

    Article  CAS  PubMed  Google Scholar 

  • Brummelkamp TR, Bernards R, Agami R (2002) A system for stable expression of short interfering RNAs in mammalian cells. Science 296:550–553

    Article  CAS  PubMed  Google Scholar 

  • Cerutti L, Mian N, Bateman A (2000) Domains in gene silencing and cell differentiation proteins: the novel PAZ domain and redefinition of the Piwi domain. Trends Biochem Sci 25:481–482

    Article  CAS  PubMed  Google Scholar 

  • Chase D, Serafinas C, Ashcroft N, Kosinski M, Longo D, Ferris DK, Golden A (2000) The polo-like kinase PLK-1 is required for nuclear envelope breakdown and the completion of meiosis in Caenorhabditis elegans. Genesis 26:26–41

    Article  CAS  PubMed  Google Scholar 

  • Chicas A, Macino G (2001) Characteristics of posttranscriptional gene silencing. EMBO Rep 2:992–996

    Article  CAS  PubMed  Google Scholar 

  • Chiu YL, Rana TM (2002) RNAi in human cells: basic structural and functional features of small interfering RNA. Mol Cell 10:549–561

    CAS  PubMed  Google Scholar 

  • Clemens MJ (1997) Pkr: a protein kinase regulated by double-stranded RNA. Int J Biochem Cell Biol 29:945–949

    Article  CAS  PubMed  Google Scholar 

  • Clemens MJ, Elia A (1997) The double-stranded RNA-dependent protein kinase PKR: structure and function. J Interferon Cytokine Res17:503–524

    Google Scholar 

  • Cogoni CM, Macino G (1997) Isolation of quelling-defective (QDE) mutants impaired in posttranscriptional transgene-induced gene silencing in Neurospora crassa. Proc Natl Acad Sci USA 94:10233–10238

    Article  CAS  PubMed  Google Scholar 

  • Cogoni C, Macino G (1999) Gene silencing in Neurospora crassa requires a protein homologous to RNA-dependent RNA polymerase. Nature 399:166–169

    CAS  PubMed  Google Scholar 

  • Dalmay T, Hamilton A, Rudd S, Angell S, Baulcombe DC (2000) An RNA-dependent RNA polymerase gene in Arabidopsis is required for posttranscriptional gene silencing mediated by a transgene but not by a virus. Cell 101:543–553

    CAS  PubMed  Google Scholar 

  • Dalmay T, Horsefield R, Braunstein TH, Baulcombe DC (2001) SDE3 encodes an RNA helicase required for posttranscriptional gene silencing in Arabidopsis. EMBO J 20:2069–2077

    Article  CAS  PubMed  Google Scholar 

  • Diallo M, Arenz C, Schmitz K, Sandhoff K, Schepers U (2003) RNA interference: a new method to analyze the function of glycoproteins and glycosylating proteins. Knock-out experiments with UDP-glucose ceramide glucosyltransferase as an example for its general application. Methods Enzymol 363:173–190

    Google Scholar 

  • Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T (2001a) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411:494–498

    Google Scholar 

  • Elbashir SM, Martinez J, Patkaniowska A, Lendeckel W, Tuschl T (2001b) Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate. EMBO J 20:6877–6888

    Article  CAS  PubMed  Google Scholar 

  • Fire A, Xu SQ, Montgomery MK, Kostas SA, Driver SE, Mello CC (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391:806–811

    CAS  PubMed  Google Scholar 

  • Gitlin L, Karelsky S, Andino R (2002) Short interfering RNA confers intracellular antiviral immunity in human cells. Nature 418:430–434

    Article  CAS  PubMed  Google Scholar 

  • Grishok A, Pasquinelli AE, Conte D, Li N, Parrish S, Ha I, Baillie DL, Fire A, Ruvkun G, Mello CC (2001) Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell 106:23–34

    CAS  PubMed  Google Scholar 

  • Guo S, Kemphues KJ (1995) Par-1, a gene required for establishing polarity in C. elegans embryos, encodes a putative Ser/Thr kinase that is asymmetrically distributed. Cell 81:611–620

    CAS  PubMed  Google Scholar 

  • Hamilton AJ, Baulcombe DC (1999) A species of small antisense RNA in posttranscriptional gene silencing in plants. Science 286:950–952

    CAS  PubMed  Google Scholar 

  • Hammond SM, Bernstein E, Beach D, Hannon GJ (2000) An RNA-directed nuclease mediates posttranscriptional gene silencing in Drosophila cells. Nature 404:293–296

    CAS  PubMed  Google Scholar 

  • Hammond SM, Boettcher S, Caudy AA, Kobayashi R, Hannon GJ (2001) Argonaute2, a link between genetic and biochemical analyses of RNAi. Science 293:1146–1150

    Article  CAS  PubMed  Google Scholar 

  • Hannon GJ (2002) RNA interference. Nature 418:244–251

    Article  CAS  PubMed  Google Scholar 

  • Hasuwa H, Kaseda K, Einarsdottir T, Okabe M (2002) Small interfering RNA and gene silencing in transgenic mice and rats. FEBS Lett 532:227–230.

    Article  CAS  PubMed  Google Scholar 

  • Hohjoh H (2002) RNA interference (RNA(i)) induction with various types of synthetic oligonucleotide duplexes in cultured human cells. FEBS Lett 521:195–199

    Article  CAS  PubMed  Google Scholar 

  • Hutvagner GM, Mlynarova L, Nap JP (2000) Detailed characterization of the posttranscriptional gene-silencing-related small RNA in a GUS gene-silenced tobacco. RNA 6:1445–1454

    Google Scholar 

  • Hutvagner G, Zamore PD (2002a) A microRNA in a multiple-turnover RNAi enzyme complex. Science 297:60

    Article  PubMed  Google Scholar 

  • Hutvagner G, Zamore PD (2002b) RNAi: nature abhors a double-strand. Curr Opin Genet Dev 12:225–232

    Article  CAS  PubMed  Google Scholar 

  • Hutvagner G, McLachlan J, Pasquinelli AE, Balint E, Tuschl T, Zamore PD (2001) A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science 293:834–838

    Article  CAS  PubMed  Google Scholar 

  • Ilves H, Barske C, Junker U, Bohnlein E, Veres G (1996) Retroviral vectors designed for targeted expression of RNA polymerase III-driven transcripts: a comparative study. Gene 171:203–208

    Article  CAS  PubMed  Google Scholar 

  • Jacobsen SE, Running MP, Meyerowitz EM (1999) Disruption of an RNA helicase/RNAse III gene in Arabidopsis causes unregulated cell division in floral meristems. Development 126:5231–5243

    CAS  PubMed  Google Scholar 

  • Jacque JM, Triques K, Stevenson M (2002) Modulation of HIV-1 replication by RNA interference. Nature 418:435–438

    Article  CAS  PubMed  Google Scholar 

  • Jennings PA, Molloy PL (1987) Inhibition of SV40 replicon function by engineered antisense RNA transcribed by RNA polymerase III. EMBO J 6:3043–3047

    CAS  PubMed  Google Scholar 

  • Kamath RS, et al (2003) Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature 421:231–237

    Article  CAS  PubMed  Google Scholar 

  • Kennerdell JR, Carthew RW (1998) Use of dsRNA-mediated genetic interference to demonstrate that frizzled and frizzled 2 act in the wingless pathway. Cell 95:1017–1026

    CAS  PubMed  Google Scholar 

  • Ketting RF, Fischer SE, Bernstein E, Sijen T, Hannon GJ, Plasterk RH (2001) Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes Dev 15:2654–2659

    Article  CAS  PubMed  Google Scholar 

  • Krichevsky AM, Kosik KS (2002) RNAi functions in cultured mammalian neurons. Proc Natl Acad Sci USA 99:11926–11929

    Article  CAS  PubMed  Google Scholar 

  • Lander ES, et al (2001) Initial sequencing and analysis of the human genome. Nature 409:860–921

    CAS  PubMed  Google Scholar 

  • Lee NS, Dohjima T, Bauer G, Li H, Li MJ, Ehsani A, Salvaterra P, Rossi J (2002) Expression of small interfering RNAs targeted against HIV-1 rev transcripts in human cells. Nat Biotechnol 20:500–505

    CAS  PubMed  Google Scholar 

  • Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75:843–854

    CAS  PubMed  Google Scholar 

  • Li HW, Lucy AP, Guo HS, Li WX, Ji LH, Wong SM, Ding SW (1999) Strong host resistance targeted against a viral suppressor of the plant gene silencing defence mechanism. EMBO J 18:2683–2691

    Article  CAS  PubMed  Google Scholar 

  • Li WX, Ding SW (2001) Viral suppressors of RNA silencing. Curr Opin Biotechnol 12:150–154.

    Article  CAS  PubMed  Google Scholar 

  • Lipardi C, Wei Q, Paterson BM (2001) RNAi as random degradative PCR: siRNA primers convert mRNA into dsRNAs that are degraded to generate new siRNAs. Cell 107:297–307

    CAS  PubMed  Google Scholar 

  • Maeda I, Kohara Y, Yamamoto M, Sugimoto A (2001) Large-scale analysis of gene function in Caenorhabditis elegans by high- throughput RNAi. Curr Biol 11:171–176

    Article  CAS  PubMed  Google Scholar 

  • Mallory AC, Parks G, Endres MW, Baulcombe D, Bowman LH, Pruss GJ, Vance VB (2002) The amplicon-plus system for high-level expression of transgenes in plants. Nat Biotechnol 20:622–625

    Article  CAS  PubMed  Google Scholar 

  • Martens H, Novotny J, Oberstrass J, Steck TL, Postlethwait P, Nellen W (2002) RNAi in Dictyostelium: the role of RNA-directed RNA polymerases and double-stranded RNase. Mol Biol Cell 13:445–453

    Article  CAS  PubMed  Google Scholar 

  • Martienssen RA, Colot V (2001) DNA methylation and epigenetic inheritance in plants and filamentous fungi. Science 293:1070–1074

    Article  CAS  PubMed  Google Scholar 

  • Martinez J, Patkaniowska A, Urlaub H, Luhrmann R, Tuschl T (2002) Single-stranded antisense siRNAs guide target RNA cleavage in RNAi. Cell 110:563–574

    CAS  PubMed  Google Scholar 

  • McCaffrey AP, Meuse L, Pham TTT, Conklin DS, Hannon GJ, Kay MA (2002) Gene expression: RNA interference in adult mice. Nature 418:38–39

    Article  CAS  PubMed  Google Scholar 

  • Mian IS (1997) Comparative sequence analysis of ribonucleases HII, III, II PH and D. Nucleic Acids Res 25:3187–3195

    CAS  PubMed  Google Scholar 

  • Misquitta L, Paterson BM (1999) Targeted disruption of gene function in Drosophila by RNA interference (RNA-i): a role for nautilus in embryonic somatic muscle formation. Proc Natl Acad Sci USA 96:1451–1456

    Article  CAS  PubMed  Google Scholar 

  • Miyagishi M, Taira K (2002) U6 promoter driven siRNAs with four uridine 3′ overhangs efficiently suppress targeted gene expression in mammalian cells. Nat Biotechnol 20:497–500

    Article  CAS  PubMed  Google Scholar 

  • Moss EG, Lee RC, Ambros V (1997) The cold shock domain protein LIN-28 controls developmental timing in C. elegans and is regulated by the lin-4 RNA. Cell 88:637–646

    Article  CAS  PubMed  Google Scholar 

  • Mourrain P, et al (2000) Arabidopsis SGS2 and SGS3 genes are required for posttranscriptional gene silencing and natural virus resistance. Cell 101:533–542

    CAS  PubMed  Google Scholar 

  • Nagy A (2000) Cre recombinase: the universal reagent for genome tailoring. Genesis 26:99–109

    CAS  PubMed  Google Scholar 

  • Napoli C, Lemieux C, Jorgensen R (1990) Introduction of a chimeric chalcone synthase gene into Petunia results in reversible co-suppression of homologous genes in trans. Plant Cell 2:279–289

    CAS  Google Scholar 

  • Nicholson RH, Nicholson AW (2002) Molecular characterization of a mouse cDNA encoding Dicer, a ribonuclease III ortholog involved in RNA interference. Mamm Genome 13:67–73

    Article  CAS  PubMed  Google Scholar 

  • Nishikura K (2001) A short primer on RNAi: RNA-directed RNA polymerase acts as a key catalyst. Cell 107:415–418

    PubMed  Google Scholar 

  • Novina CD, et al (2002) siRNA-directed inhibition of HIV-1 infection. Nat Med 8:681–686

    CAS  PubMed  Google Scholar 

  • Nykänen A, Haley B, Zamore PD (2001) ATP requirements and small interfering RNA structure in the RNA interference pathway. Cell 107:309–321

    PubMed  Google Scholar 

  • Ojwang JO, Hampel A, Looney DJ, Wong-Staal F, Rappaport J (1992) Inhibition of human immunodeficiency virus type 1 expression by a hairpin ribozyme. Proc Natl Acad Sci USA 89:10802–10806

    CAS  PubMed  Google Scholar 

  • Olsen PH, Ambros V (1999) The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Dev Biol 216:671–680

    Google Scholar 

  • Orr RM (2001) Technology evaluation: fomivirsen, Isis Pharmaceuticals Inc/CIBA vision. Curr Opin Mol Ther 3:288–294

    CAS  PubMed  Google Scholar 

  • Paddison PJ, Caudy AA, Bernstein E, Hannon GJ, Conklin DS (2002) Short hairpin RNAs (shRNAs) induce sequence-specific silencing in mammalian cells. Genes Dev 16:948–958

    Article  CAS  PubMed  Google Scholar 

  • Palauqui JC, Elmayan T, Pollien JM, Vaucheret H (1997) Systemic acquired silencing: transgene-specific posttranscriptional silencing is transmitted by grafting from silenced stocks to non- silenced scions. EMBO J 16:4738–4745

    Article  CAS  PubMed  Google Scholar 

  • Parrish S, Fleenor J, Xu SQ, Mello C, Fire A (2000) Functional anatomy of a dsRNA trigger: differential requirement for the two trigger strands in RNA interference. Mol Cell 6:1077–1087

    CAS  PubMed  Google Scholar 

  • Paul CP, Good PD, Winer I, Engelke DR (2002) Effective expression of small interfering RNA in human cells. Nat Biotechnol 20:505–508

    Article  CAS  PubMed  Google Scholar 

  • Plasterk RHA (2002) RNA silencing: the genome's immune system. Science 296:1263–1265

    Article  CAS  PubMed  Google Scholar 

  • Provost P, Dishart D, Doucet J, Frendewey D, Samuelsson B, Radmark O (2002) Ribonuclease activity and RNA binding of recombinant human Dicer. EMBO J 21:5864–5874

    Article  CAS  PubMed  Google Scholar 

  • Qiao L, Lissemore JL, Shu P, Smardon A, Gelber MB, Maine EM (1995) Enhancers of glp-1, a gene required for cell-signaling in Caenorhabditis elegans, define a set of genes required for germline development. Genetics 141:551–569

    CAS  PubMed  Google Scholar 

  • Reinhart BJ, Bartel DP (2002) Small RNAs correspond to centromere heterochromatic repeats. Science 297:1831

    Article  CAS  PubMed  Google Scholar 

  • Reinhart BJ, Weinstein EG, Rhoades MW, Bartel B, Bartel DP (2002a) MicroRNAs in plants. Genes Dev 16:1616–1626

  • Robertson HD, Webster RE, Zinder ND (1968) Purification and properties of ribonuclease III from Escherichia coli. J Biol Chem 243:82–91

    CAS  PubMed  Google Scholar 

  • Rotondo G, Frendewey D (1996) Purification and characterization of the Pac1 ribonuclease of Schizosaccharomyces pombe. Nucleic Acids Res 24:2377–2386

    Article  CAS  PubMed  Google Scholar 

  • Sango K, Yamanaka S, Hoffmann A, Okuda Y, Grinberg A, Westphal H, McDonald MP, Crawley JN, Sandhoff K, Suzuki K, et al (1995) Mouse models of Tay-Sachs and Sandhoff diseases differ in neurologic phenotype and ganglioside metabolism. Nat Genet 11:170–176

    CAS  PubMed  Google Scholar 

  • Schepers U, Kolter T (2001) RNA interference: a new way to analyze protein function. Angew Chem Int Ed 40:2437–2439

    Article  CAS  Google Scholar 

  • Schumacher JM, Golden A, Donovan PJ (1998) AIR-2: an Aurora/Ip11-related protein kinase associated with chromosomes and midbody microtubules is required for polar body extrusion and cytokinesis in Caenorhabditis elegans embryos. J Cell Biol 143:1635–1646

    CAS  PubMed  Google Scholar 

  • Schwarz DS, Hutvagner G, Haley B, Zamore PD (2002) Evidence that siRNAs function as guides, not primers, in the Drosophila and human RNAi pathways. Mol Cell 10:537–548

    CAS  PubMed  Google Scholar 

  • Sczakiel G, Far RK (2002) The role of target accessibility for antisense inhibition. Curr Opin Mol Ther 4:149–153

    CAS  PubMed  Google Scholar 

  • Seggerson K, Tang LJ, Moss EG (2002) Two genetic circuits repress the Caenorhabditis elegans heterochronic gene lin-28 after translation initiation. Dev Biol 243:215–225

    Article  CAS  PubMed  Google Scholar 

  • Sijen T, Fleenor J, Simmer F, Thijssen KL, Parrish S, Timmons L, Plasterk RHA, Fire A (2001) On the role of RNA amplification in dsRNA-triggered gene silencing. Cell 107:465–476

    CAS  PubMed  Google Scholar 

  • Smardon A, Spoerke JM, Stacey SC, Klein ME, Mackin N, Maine EM (2000) EGO-1 is related to RNA-directed RNA polymerase and functions in germ- line development and RNA interference in C. elegans. Curr Biol 10:169–178

    CAS  PubMed  Google Scholar 

  • Sui G, Soohoo C, Affar el B, Gay F, Shi Y, Forrester WC (2002) A DNA vector-based RNAi technology to suppress gene expression in mammalian cells. Proc Natl Acad Sci USA 99:5515–5520

    Article  CAS  PubMed  Google Scholar 

  • Sullenger BA, Gallardo HF, Ungers GE, Gilboa E (1990) Overexpression of TAR sequences renders cells resistant to human immunodeficiency virus replication. Cell 63:601–608

    CAS  PubMed  Google Scholar 

  • Tabara H, Grishok A, Mello CC (1998) Rnai in C. elegans: soaking in the genome sequence. Science 282:430–431

    Article  CAS  PubMed  Google Scholar 

  • Tabara H, Sarkissian M, Kelly WG, Fleenor J, Grishok A, Timmons L, Fire A, Mello CC (1999) The rde-1 gene, RNA interference, and transposon silencing in C. elegans. Cell 99:123–132

    CAS  PubMed  Google Scholar 

  • Tabara H, Yigit E, Siomi H, Mello CC (2002) The dsRNA binding protein RDE-4 interacts with RDE-1, DCR-1, and a DExH- box helicase to direct RNAi in C. elegans. Cell 109:861–871

    CAS  PubMed  Google Scholar 

  • Tijsterman M, Ketting RF, Okihara KL, Sijen T, Plasterk RHA (2002) RNA helicase MUT-14-dependent gene silencing triggered in C. elegans by short antisense RNAs. Science 295:694–697

    Article  CAS  PubMed  Google Scholar 

  • Tuschl T, Borkhardt A (2002) Small interfering RNAs: a revolutionary tool for the analysis of gene function and gene therapy. Mol Interv 2:158–167

    Article  CAS  Google Scholar 

  • Tuschl T, Zamore PD, Lehmann R, Bartel DP, Sharp PA (1999) Targeted mRNA degradation by double-stranded RNA in vitro. Genes Dev 13:3191–3197

    CAS  PubMed  Google Scholar 

  • Vaucheret H, Beclin C, Fagard M (2001) Posttranscriptional gene silencing in plants. J Cell Sci 114:3083–3091

    CAS  PubMed  Google Scholar 

  • Venter JC, et al (2001) The sequence of the human genome. Science 291:1304–1351

    CAS  PubMed  Google Scholar 

  • Voinnet O, Pinto YM, Baulcombe DC (1999) Suppression of gene silencing: a general strategy used by diverse DNA and RNA viruses of plants. Proc Natl Acad Sci USA 96:14147–14152

    Article  CAS  PubMed  Google Scholar 

  • Volpe TA, Kidner C, Hall IM, Teng G, Grewal SIS, Martienssen RA (2002) Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science 297:1833–1837

    CAS  PubMed  Google Scholar 

  • Wianny F, Zernicka-Goetz M (2000) Specific interference with gene function by double-stranded RNA in early mouse development. Nat Cell Biol 2:70–75

    Article  CAS  PubMed  Google Scholar 

  • Wightman B, Ha I, Ruvkun G (1993) Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 75:855–862

    CAS  PubMed  Google Scholar 

  • Yang D, Lu H, Erickson JW (2000) Evidence that processed small dsRNAs may mediate sequence-specific mRNA degradation during RNAi in Drosophila embryos. Curr Biol 10:1191–1200

    CAS  PubMed  Google Scholar 

  • Yi CE, Bekker JM, Miller G, Hill KL, Crosbie RH (2003) Specific and potent RNA interference in terminally differentiated myotubes. J Biol Chem 278:934–939

    Article  CAS  PubMed  Google Scholar 

  • Yu JY, DeRuiter SL, Turner DL (2002) RNA interference by expression of short-interfering RNAs and hairpin RNAs in mammalian cells. Proc Natl Acad Sci USA 99:6047–6052

    Article  CAS  PubMed  Google Scholar 

  • Zamore PD (2001a) Thirty-three years later, a glimpse at the ribonuclease III active site. Mol Cell 8:1158–1160

    CAS  PubMed  Google Scholar 

  • Zamore PD (2001b) RNA interference: listening to the sound of silence. Nat Struct Biol 8:746–750

    Article  CAS  PubMed  Google Scholar 

  • Zamore PD, Tuschl T, Sharp PA, Bartel DP (2000) RNAi: double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell 101:25–33

    CAS  PubMed  Google Scholar 

  • Zeng Y, Wagner EJ, Cullen BR (2002) Both natural and designed micro RNAs technique can inhibit the expression of cognate mRNAs when expressed in human cells. Mol Cell 9:1327–1333

    CAS  PubMed  Google Scholar 

  • Zhang H, Kolb FA, Brondani V, Billy E, Filipowicz W (2002) Human Dicer preferentially cleaves dsRNAs at their termini without a requirement for ATP. EMBO J 21:5875–5885

    Article  CAS  PubMed  Google Scholar 

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  1. Kekulé-Institut für Organische Chemie und Biochemie, Universität Bonn, Gerhard Domagk Strasse 1, 53121, Bonn, Germany

    Christoph Arenz & Ute Schepers

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Arenz, C., Schepers, U. RNA interference: from an ancient mechanism to a state of the art therapeutic application?. Naturwissenschaften 90, 345–359 (2003). https://doi.org/10.1007/s00114-003-0441-4

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