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RNAi Pathway in C. elegans: The Argonautes and Collaborators

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RNA Interference

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 320))

Abstract

Since Dr. Sidney Brenner first used it as an animal model system, the round worm Caenorhabditis elegans has significantly contributed to our understanding of important biological processes. Among them, the discovery in the 1990s of new gene silencing pathways orchestrated by tiny non-coding RNAs created a new field of research in biology. In this review, we will discuss the key players of the RNAi path-ways in C. elegans and particularly the Argonaute genes, an impressive gene family of 27 members important in many aspects of these pathways.

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References

  • Ambros V, Lee RC, Lavanway A, Williams PT, Jewell D (2003) MicroRNAs and other tiny endogenous RNAs in C. elegans. Curr Biol 13:807–818.

    Article  PubMed  Google Scholar 

  • Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297.

    Article  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.

    Article  PubMed  Google Scholar 

  • Carmell MA, Xuan Z, Zhang MQ, Hannon GJ (2002) The Argonaute family: tentacles that reach into RNAi, developmental control, stem cell maintenance, and tumorigenesis. Genes Dev 16:2733–2742.

    Article  PubMed  Google Scholar 

  • Chen CC, Simard MJ, Tabara H, Brownell DR, McCollough JA, Mello CC (2005) A member of the polymerase beta nucleotidyltransferase superfamily is required for RNA interference in C. elegans. Curr Biol 15:378–383.

    Article  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.

    Article  PubMed  Google Scholar 

  • Cox DN, Chao A, Baker J, Chang L, Qiao D, Lin H (1998) A novel class of evolutionarily conserved genes defined by piwi are essential for stem cell self-renewal. Genes Dev 12:3715–3727.

    Article  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.

    Article  PubMed  Google Scholar 

  • Deshpande T, Takagi T, Hao L, Buratowski S, Charbonneau H (1999) Human PIR1 of the protein-tyrosine phosphatase superfamily has RNA 5′-triphosphatase and diphosphatase activities. J Biol Chem 274:16590–16594.

    Article  PubMed  Google Scholar 

  • Domeier ME, Morse DP, Knight SW, Portereiko M, Bass BL, Mango SE (2000) A link between RNA interference and nonsense-mediated decay in Caenorhabditis elegans. Science 289:1928–1931.

    Article  PubMed  Google Scholar 

  • Duchaine TF, Wohlschlegel JA, Kennedy S, Bei Y, Conte D Jr, Pang K, Brownell DR, Harding S, Mitani S, Ruvkun G, et al (2006) Functional proteomics reveals the biochemical niche of C. elegans DCR-1 in multiple small-RNA-mediated pathways. Cell 124:343–354.

    Article  PubMed  Google Scholar 

  • Feinberg EH, Hunter CP (2003) Transport of dsRNA into cells by the transmembrane protein SID-1. Science 301:1545–1547.

    Article  PubMed  Google Scholar 

  • Fire A, Xu S, 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.

    Article  PubMed  Google Scholar 

  • Grishok A, Tabara H, Mello CC (2000) Genetic requirements for inheritance of RNAi in C. elegans. Science 287:2494–2497.

    Article  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.

    Article  PubMed  Google Scholar 

  • Grishok A, Sinskey JL, Sharp PA (2005) Transcriptional silencing of a transgene by RNAi in the soma of C. elegans. Genes Dev 19:683–696.

    Article  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.

    Article  PubMed  Google Scholar 

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

    Article  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  PubMed  Google Scholar 

  • Hutvágner G, Simard MJ, Mello CC, Zamore PD (2004) Sequence-specific inhibition of small RNA function. PLoS Biol 2:E98.

    Article  PubMed  Google Scholar 

  • Kennedy S, Wang D, Ruvkun G (2004) A conserved siRNA-degrading RNase negatively regulates RNA interference in C. elegans. Nature 427:645–649.

    Article  PubMed  Google Scholar 

  • Ketting RF, Plasterk RH (2000) A genetic link between co-suppression and RNA interference in C. elegans. Nature 404:296–298.

    Article  PubMed  Google Scholar 

  • Ketting RF, Haverkamp TH, van Luenen HG, Plasterk RH (1999) Mut-7 of C. elegans, required for transposon silencing and RNA interference, is a homolog of Werner syndrome helicase and RNaseD. Cell 99:133–141.

    Article  PubMed  Google Scholar 

  • Knight SW, Bass BL (2001) A role for the RNase III enzyme DCR-1 in RNA interference and germ line development in Caenorhabditis elegans. Science 293:2269–2271.

    Article  PubMed  Google Scholar 

  • Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T (2001) Identification of novel genes coding for small expressed RNAs. Science 294:853–858.

    Article  PubMed  Google Scholar 

  • Lau NC, Lim LP, Weinstein EG, Bartel DP (2001) An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 294:858–862.

    Article  PubMed  Google Scholar 

  • Lee RC, Ambros V (2001) An extensive class of small RNAs in Caenorhabditis elegans. Science 294:862–864.

    Article  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.

    Article  PubMed  Google Scholar 

  • Lee RC, Hammell CM, Ambros V (2006) Interacting endogenous and exogenous RNAi pathways in Caenorhabditis elegans. Rna 12:589–597.

    Article  PubMed  Google Scholar 

  • Liu J, Carmell MA, Rivas FV, Marsden CG, Thomson JM, Song JJ, Hammond SM, Joshua-Tor L, Hannon GJ (2004) Argonaute2 is the catalytic engine of mammalian RNAi. Science 305:1437–1441.

    Article  PubMed  Google Scholar 

  • Lu R, Maduro M, Li F, Li HW, Broitman-Maduro G, Li WX, Ding SW (2005) Animal virus replication and RNAi-mediated antiviral silencing in Caenorhabditis elegans. Nature 436:1040–1043.

    Article  PubMed  Google Scholar 

  • Ma JB, Yuan YR, Meister G, Pei Y, Tuschl T, Patel DJ (2005) Structural basis for 5c-end-specific recognition of guide RNA by the A. fulgidus Piwi protein. Nature 434:666–670.

    Article  PubMed  Google Scholar 

  • Meister G, Landthaler M, Patkaniowska A, Dorsett Y, Teng G, Tuschl T (2004) Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol Cell 15:185–197.

    Article  PubMed  Google Scholar 

  • Mourrain P, Beclin C, Elmayan T, Feuerbach F, Godon C, Morel JB, Jouette D, Lacombe AM, Nikic S, Picault N, et al (2000) Arabidopsis SGS2 and SGS3 genes are required for posttranscriptional gene silencing and natural virus resistance. Cell 101:533–542.

    Article  PubMed  Google Scholar 

  • Okamura K, Ishizuka A, Siomi H, Siomi MC (2004) Distinct roles for Argonaute proteins in small RNA-directed RNA cleavage pathways. Genes Dev 18:1655–1666.

    Article  PubMed  Google Scholar 

  • Pak J, Fire A (2007) Distinct populations of primary and secondary effectors during RNAi in C. elegans. Science 315:241–244.

    Article  PubMed  Google Scholar 

  • Parker JS, Roe SM, Barford D (2005) Structural insights into mRNA recognition from a PIWI domain-siRNA guide complex. Nature 434:663–666.

    Article  PubMed  Google Scholar 

  • Parrish S, Fire A (2001) Distinct roles for RDE-1 and RDE-4 during RNA interference in Caenorhabditis elegans. Rna 7:1397–1402.

    PubMed  Google Scholar 

  • Pasquinelli AE, Reinhart BJ, Slack F, Martindale MQ, Kuroda MI, Maller B, Hayward DC, Ball EE, Degnan B, Muller P, et al (2000) Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature 408:86–89.

    Article  PubMed  Google Scholar 

  • Reinhart BJ, Slack FJ, Basson M, Pasquinelli AE, Bettinger JC, Rougvie AE, Horvitz HR, Ruvkun G (2000) The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403:901–906.

    Article  PubMed  Google Scholar 

  • Rivas FV, Tolia NH, Song JJ, Aragon JP, Liu J, Hannon GJ, Joshua-Tor L (2005) Purified Argonaute2 and an siRNA form recombinant human RISC. Nat Struct Mol Biol 12:340–349.

    Article  PubMed  Google Scholar 

  • Rocheleau CE, Downs WD, Lin R, Wittmann C, Bei Y, Cha YH, Ali M, Priess JR, Mello CC (1997) Wnt signaling and an APC-related gene specify endoderm in early C. elegans embryos. Cell 90:707–716.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Sijen T, Steiner FA, Thijssen KL, Plasterk RH (2007) Secondary siRNAs result from unprimed RNA synthesis and form a distinct class. Science 315:244–247.

    Article  PubMed  Google Scholar 

  • Simmer F, Tijsterman M, Parrish S, Koushika SP, Nonet ML, Fire A, Ahringer J, Plasterk RH (2002) Loss of the putative RNA-directed RNA polymerase RRF-3 makes C. elegans hypersensitive to RNAi. Curr Biol 12:1317–1319.

    Article  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.

    Article  PubMed  Google Scholar 

  • Song JJ, Joshua-Tor L (2006) Argonaute and RNA-getting into the groove. Curr Opin Struct Biol 16:5–11.

    Article  PubMed  Google Scholar 

  • Song JJ, Smith SK, Hannon GJ, Joshua-Tor L (2004) Crystal structure of Argonaute and its implications for RISC slicer activity. Science 305:1434–1437.

    Article  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.

    Article  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.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Tolia NH, Joshua-Tor L (2007) Slicer and the argonautes. Nat Chem Biol 3:36–43.

    Article  PubMed  Google Scholar 

  • Vastenhouw NL, Plasterk RH (2004) RNAi protects the Caenorhabditis elegans germline against transposition. Trends Genet 20:314–319.

    Article  PubMed  Google Scholar 

  • Vastenhouw NL, Fischer SE, Robert VJ, Thijssen KL, Fraser AG, Kamath RS, Ahringer J, Plasterk RH (2003) A genome-wide screen identifies 27 genes involved in transposon silencing in C. elegans. Curr Biol 13:1311–1316.

    Article  PubMed  Google Scholar 

  • Vastenhouw NL, Brunschwig K, Okihara KL, Muller F, Tijsterman M, Plasterk RH (2006) Gene expression: long-term gene silencing by RNAi. Nature 442:882.

    Article  PubMed  Google Scholar 

  • Wilkins C, Dishongh R, Moore SC, Whitt MA, Chow M, Machaca K (2005) RNA interference is an antiviral defence mechanism in Caenorhabditis elegans. Nature 436:1044–1047.

    Article  PubMed  Google Scholar 

  • Winston WM, Molodowitch C, Hunter CP (2002) Systemic RNAi in C. elegans requires the putative transmembrane protein SID-1. Science 295:2456–2459.

    Article  PubMed  Google Scholar 

  • Yigit E, Batista PJ, Bei Y, Pang KM, Chen CC, Tolia NH, Joshua-Tor L, Mitani S, Simard MJ, Mello CC (2006) Analysis of the C. elegans Argonaute family reveals that distinct Argonautes act sequentially during RNAi. Cell 127:747–757.

    Article  PubMed  Google Scholar 

  • Yuan Y, Li DM, Sun H (1998) PIR1, a novel phosphatase that exhibits high affinity to RNA ribonucleoprotein complexes. J Biol Chem 273:20347–20353.

    Article  PubMed  Google Scholar 

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Boisvert, ME., Simard, M.J. (2008). RNAi Pathway in C. elegans: The Argonautes and Collaborators. In: Paddison, P.J., Vogt, P.K. (eds) RNA Interference. Current Topics in Microbiology and Immunology, vol 320. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-75157-1_2

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