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On the origin and functions of RNA-mediated silencing: from protists to man

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Abstract

Double-stranded RNA has been shown to induce gene silencing in diverse eukaryotes and by a variety of pathways. We have examined the taxonomic distribution and the phylogenetic relationship of key components of the RNA interference (RNAi) machinery in members of five eukaryotic supergroups. On the basis of the parsimony principle, our analyses suggest that a relatively complex RNAi machinery was already present in the last common ancestor of eukaryotes and consisted, at a minimum, of one Argonaute-like polypeptide, one Piwi-like protein, one Dicer, and one RNA-dependent RNA polymerase. As proposed before, the ancestral (but non-essential) role of these components may have been in defense responses against genomic parasites such as transposable elements and viruses. From a mechanistic perspective, the RNAi machinery in the eukaryotic ancestor may have been capable of both small-RNA-guided transcript degradation as well as transcriptional repression, most likely through histone modifications. Both roles appear to be widespread among living eukaryotes and this diversification of function could account for the evolutionary conservation of duplicated Argonaute-Piwi proteins. In contrast, additional RNAi-mediated pathways such as RNA-directed DNA methylation, programmed genome rearrangements, meiotic silencing by unpaired DNA, and miRNA-mediated gene regulation may have evolved independently in specific lineages.

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References

  • Abed M, Ankri S (2005) Molecular characterization of Entamoeba histolytica RNase III and AGO2, two RNA interference hallmark proteins. Exp Parasitol 110:265–269

    PubMed  CAS  Google Scholar 

  • Adl SM, Simpson AGB, Farmer MA, Andersen RA, Anderson OR, Barta JR, Bowser SS, Brugerolle G, Fensome RA, Fredericq S, James TY, Karpov S, Kugrens P, Krug J, Lane CE, Lewis LA, Lodge J, Lynn DH, Mann DG, McCourt RM, Mendoza L, Moestrup O, Mozley-Standridge SE, Nerad TA, Shearer CA, Smirnov AV, Spiegel FW, Taylor MFJR (2005) The new higher level classification of eukaryotes with emphasis on the taxonomy of protists. J Eukaryot Microbiol 52:399–451

    PubMed  Google Scholar 

  • Allen E, Xie Z, Gustafson AM, Sung GH, Spatafora JW, Carrington JC (2004) Evolution of microRNA genes by inverted duplication of target gene sequences in Arabidopsis thaliana. Nat Genet 36:1282–1290

    PubMed  CAS  Google Scholar 

  • Allen E, Xie Z, Gustafson AM, Carrington JC (2005) microRNA-directed phasing during trans-acting siRNA biogenesis in plants. Cell 121:207–221

    PubMed  CAS  Google Scholar 

  • An CI, Sawada A, Fukusaki E, Kobayashi A (2003) A transient RNA interference assay system using Arabidopsis protoplasts. Biosci Biotechnol Biochem 67:2674–2677

    PubMed  CAS  Google Scholar 

  • Anantharaman V, Koonin EV, Aravind L (2002) Comparative genomics and evolution of proteins involved in RNA metabolism. Nucleic Acids Res 30:1427–1464

    PubMed  CAS  Google Scholar 

  • Aravin AA, Lagos-Quintana M, Yalcin A, Zavolan M, Marks D, Snyder B, Gaasterland T, Meyer J, Tuschl T (2003) The small RNA profile during Drosophila melanogaster development. Dev Cell 5:337–350

    PubMed  CAS  Google Scholar 

  • Aravin AA, Klenov MS, Vagin VV, Bantignies F, Cavalli G, Gvozdev VA (2004) Dissection of a natural RNA silencing process in the Drosophila melanogaster germ line. Mol Cell Biol 24:6742–6750

    PubMed  CAS  Google Scholar 

  • Arisue N, Hasegawa M, Hashimoto T (2004) Root of the Eukaryota tree as inferred from combined maximum likelihood analyses of multiple molecular sequence data. Mol Biol Evol 22:409–420

    PubMed  Google Scholar 

  • Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:282–297

    Google Scholar 

  • Baulcombe D (2004) RNA silencing in plants. Nature 431:356–363

    PubMed  CAS  Google Scholar 

  • Baumberger N, Baulcombe DC (2005) Arabidopsis ARGONAUTE1 is an RNA slicer that selectively recruits microRNAs and short interfering RNAs. Proc Natl Acad Sci USA 102:11928–11933

    PubMed  CAS  Google Scholar 

  • Bentwich I, Avniel A, Karov Y, Aharonov R, Gilad S, Barad O, Barzilai A, Einat P, Einav U, Meiri E, Sharon E, Spector Y, Bentwich Z (2005) Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet 37:766–770

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Buchon N, Vaury C (2006) RNAi: a defensive RNA-silencing against viruses and transposable elements. Heredity 96:195–202

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Carrington JC, Ambros V (2003) Role of microRNAs in plant and animal development. Science 301:336–338

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Chan SW, Zilberman D, Xie Z, Johansen LK, Carrington JC, Jacobsen SE (2004) RNA silencing genes control de novo DNA methylation. Science 303:1336

    PubMed  CAS  Google Scholar 

  • Chen X (2005) microRNA biogenesis and function in plants. FEBS Lett 579:5923–5931

    PubMed  CAS  Google Scholar 

  • Chicas A, Cogoni C, Macino G (2004) RNAi-dependent and RNAi-independent mechanisms contribute to the silending of RIPed sequences in Neurospora crassa. Nucleic Acids Res 32:4237–4243

    PubMed  CAS  Google Scholar 

  • Chicas A, Forrest EC, Sepich S, Cogoni C, Macino G (2005) Small interfering RNAs that trigger posttranscriptional gene silencing are not required for the histone H3 Lys9 methylation necessary for tandem repeat stabilization in Neurospora crassa. Mol Cell Biol 25:3793–3801

    PubMed  CAS  Google Scholar 

  • Cogoni C, Macino G (2000) Post-transcriptional gene silencing across kingdoms. Curr Opin Genet Dev 10:638–643

    PubMed  CAS  Google Scholar 

  • Cox DN, Chao A, Lin H (2000) Piwi encodes a nucleoplasmic factor whose activity modulates the number and division rate of germline stem cells. Development 127:503–514

    PubMed  CAS  Google Scholar 

  • DaRocha WD, Otsu K, Teixeira SM, Donelson JE (2004) Tests of cytoplasmic RNA interference (RNAi) and construction of a tetracycline-inducible T7 promoter system in Trypanosoma cruzi. Mol Biochem Parasitol 133:175–186

    PubMed  CAS  Google Scholar 

  • Djikeng A, Shi H, Tschudi C, Ullu E (2001) RNA interference in Trypanosoma brucei: cloning of small interfering RNAs provides evidence for retroposon-derived 24–26-nucleotide RNAs. RNA 7:1522–1530

    PubMed  CAS  Google Scholar 

  • Durand-Dubief M, Bastin P (2003) TbAGO1, an Argonaute protein required for RNA interference is involved in mitosis and chromosome segregation in Trypanosoma brucei. BMC Biol 1:2

    PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Findley SD, Tamanaha M, Clegg NJ, Ruohola-Baker H (2003) Maelstrom, a Drosophila spindle-class gene, encodes a protein that colocalizes with Vasa and RDE1/AGO1 homolog, Aubergine, in nuage. Development 130:859–871

    PubMed  CAS  Google Scholar 

  • Farh KK, Grimson A, Jan C, Lewis BP, Johnston WK, Lim LP, Burge CB, Bartel DP (2005) The widespread impact of mammalian microRNAs on mRNA repression and evolution. Science 310:1817–1821

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Force a, Lynch M, Pickett B, Amores A, Yan Y-L (1999) Preservation of duplicate genes by complementary, degenerative mutations. Genetics 151:1531–1545

    PubMed  Google Scholar 

  • Freitag M, Lee DW, Kothe GO, Pratt RJ, Aramayo R, Selker EU (2004) DNA methylation is independent of RNA interference in Neurospora. Science 304:1939

    PubMed  CAS  Google Scholar 

  • Fukagawa T, Nogami M, Yoshikawa M, Ikeno M, Okazaki T, Takami Y, Nakayama T, Oshimura M (2004) Dicer is essential for formation of the heterochromatin structure in vertebrate cells. Nat Cell Biol 6:784–791

    PubMed  CAS  Google Scholar 

  • Fuks F (2005) DNA methylation and histone modifications: teaming up to silence genes. Curr Opin Genet Dev 15:490–495

    PubMed  CAS  Google Scholar 

  • Galvani A, Sperling L (2002) RNA interference by feeding in Paramecium. Trends Genet 18:11–12

    PubMed  CAS  Google Scholar 

  • Garnier O, Serrano V, Duharcourt S, Meyer E (2004) RNA-mediated programming of developmental genome rearrangements in Paramecium tetraurelia. Mol Cell Biol 24:7370–7379

    PubMed  CAS  Google Scholar 

  • Gesellchen V, Boutros M (2004) Managing the genome: microRNAs in Drosophila. Differentiation 72:74–80

    PubMed  Google Scholar 

  • Giraldez AJ, Cinalli RM, Glasner ME, Enright AJ, Thomson JM, Baskerville S, Hammond SM, Bartel DP, Schier AF (2005) MicroRNAs regulate brain morphogenesis in zebrafish. Science 308:833–838

    PubMed  CAS  Google Scholar 

  • Goll MG, Bestor TH (2005) Eukaryotic cytosine methyltransferases. Annu Rev Biochem 74:481–514

    PubMed  CAS  Google Scholar 

  • Grishok A, Mello CC (2002) RNAi (Nematodes: Caenorhabditis elegans). Adv Genet 46:339–360

    Article  PubMed  CAS  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

    PubMed  CAS  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

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Hammond TM, Keller NP (2005) RNA silencing in Aspergillus nidulans is independent of RNA-dependent RNA polymerases. Genetics 169:607–617

    PubMed  CAS  Google Scholar 

  • Herr AJ, Jensen MB, Dalmay T, Baulcombe DC (2005) RNA polymerase IV directs silencing of endogenous DNA. Science 308:118–120

    PubMed  CAS  Google Scholar 

  • Hoa NT, Keene KM, Olson KE, Zheng L (2003) Characterization of RNA interference in an Anopheles gambiae cell line. Insect Biochem Mol Biol 33:949–957

    PubMed  CAS  Google Scholar 

  • Humphreys DT, Westman BJ, Martin DIK, Preiss T (2005) MicroRNAs control translation initiation by inhibiting eukaryotic initiation factor 4E/cap and poly(A) tail function. Proc Natl Acad Sci USA 102:16961–16966

    PubMed  CAS  Google Scholar 

  • Jeong B-R, Wu-Scharf D, Zhang C, Cerutti H (2002) Suppressors of transcriptional transgenic silencing in Chlamydomonas are sensitive to DNA-damaging agents and reactivate transposable elements. Proc Natl Acad Sci USA 99:1076–1081

    CAS  Google Scholar 

  • Jia S, Noma K, Grewal SIS (2004) RNAi-independent heterochromatin nucleation by the stress-activated ATF/CREB family proteins. Science 304:1971–1975

    PubMed  CAS  Google Scholar 

  • Kaller M, Euteneuer U, Nellen W (2006) Differential effects of Heterochromatin Protein 1 isoforms on mitotic chromosome distribution and growth in Dictyostelium discoideum. Eukaryot Cell 5:530–543

    PubMed  CAS  Google Scholar 

  • Kanellopoulou C, Muljo SA, Kung AL, Ganesan S, Drapkin R, Jenuwein T, Livingston DM, Rajewsky K (2005) Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Genes Dev 19:489–501

    PubMed  CAS  Google Scholar 

  • Kanno T, Huettel B, Mette MF, Aufsatz W, Jaligot E, Daxinger L, Kreil DP, Matzke M, Matzke AJM (2005) Atypical RNA polymerase subunits required for RNA-directed DNA methylation. Nat Genet 37:761–765

    PubMed  CAS  Google Scholar 

  • Kaur G, Lohia A (2004) Inhibition of gene expression with double strand RNA interference in Entamoeba histolytica. Biochem Biophys Res Commun 320:1118–1122

    PubMed  CAS  Google Scholar 

  • Kavi HH, Fernandez HR, Xie W, Birchler JA (2005) RNA silencing in Drosophila. FEBS Lett 579:5940–5949

    PubMed  CAS  Google Scholar 

  • Kawasaki H, Taira K (2004) Induction of DNA methylation and gene silencing by short interfering RNAs in human cells. Nature 431:211–217

    PubMed  CAS  Google Scholar 

  • Keene KM, Foy BD, Sanchez-Vargas I, Beaty BJ, Blair CD, Olson KE (2004) RNA interference acts as a natural antiviral response to O’nyong-nyong virus (Alphavirus; Togaviridae) infection of Anopheles gambiae. Proc Natl Acad Sci USA 101:17240–17245

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Kidner CA, Martienssen RA (2005) The developmental role of miRNA in plants. Curr Opin Plant Biol 8:38–44

    PubMed  CAS  Google Scholar 

  • Kuhlmann M, Borisova BE, Kaller M, Larsson P, Stach D, Na J, Eichinger L, Lyko F, Ambros V, Söderbom F, Hammann C, Nellen W (2005) Silencing of retrotransposons in Dictyostelium by DNA methylation and RNAi. Nucleic Acids Res 19:6405–6417

    Google Scholar 

  • Kurihara Y, Watanabe Y (2004) Arabidopsis micro-RNA biogenesis through Dicer-like 1 protein functions. Proc Natl Acad Sci USA 101:12753–12758

    PubMed  CAS  Google Scholar 

  • Laayoun A, Smith SS (1995) Methylation of slipped duplexes, snapbacks and cruciforms by human DNA (cytosine-5) methyltransferase. Nucleic Acids Res 23:1584–1589

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Lagos-Quintana M, Rauhut R, Meyer J, Borkhardt A, Tuschl T (2003) New microRNAs from mouse and human. RNA 9:175–179

    PubMed  CAS  Google Scholar 

  • Lee DW, Pratt RJ, McLauhlin M, Aramayo R (2003) An Argonaute-like protein is required for meiotic silencing. Genetics 164:821–828

    PubMed  CAS  Google Scholar 

  • Lee DW, Seong K-Y, Pratt RJ, Baker K, Aramayo R (2004) Properties of unpaired DNA required for efficient silencing in Neurospora crassa. Genetics 167:131–150

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Lee SR, Collins K (2006) Two classes of endogenous small RNAs in Tetrahymena thermophila. Genes Dev 20:28–33

    PubMed  CAS  Google Scholar 

  • Li H-W, Ding S-W (2005) Antiviral silencing in animals. FEBS Lett 579:5965–5973

    PubMed  CAS  Google Scholar 

  • Li J, Yang Z, Yu B, Liu J, Chen X (2005) Methylation protects miRNAs and siRNAs from a 3′ end uridylation activity in Arabidopsis. Curr Biol 15: 1501–1507

    PubMed  CAS  Google Scholar 

  • Lim LP, Lau NC, Weinstein EG, Abdelhakim A, Yekta S, Rhoades MW, Burge CB, Bartel DP (2003) The microRNAs of Caenorhabditis elegans. Genes Dev 17:991–1008

    PubMed  CAS  Google Scholar 

  • Lingel A, Simon B, Izaurralde E, Sattler M (2004) Nucleic acid 3′-end recognition by the Argonaute2 PAZ domain. Nat Struct Mol Biol 11:576–577

    PubMed  CAS  Google Scholar 

  • Lippman Z, May B, Yordan C, Singer T, Martienssen R (2003) Distinct mechanisms determine transposon inheritance and methylation via small interfering RNA and histone modification. PLoS Biol 1:E67

    PubMed  Google Scholar 

  • Lippman Z, Martienssen R (2004) The role of RNA interference in heterochromatic silencing. Nature 431:364–370

    PubMed  CAS  Google Scholar 

  • Liu B, Li P, Li X, Liu C, Cao S, Chu C, Cao X (2005a) Loss of function of OsDCL1 affects microRNA accumulation and causes developmental defects in rice. Plant Physiol 139:296–305

    CAS  Google Scholar 

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

    CAS  Google Scholar 

  • Liu J, Rivas FV, Wohlschlegel J, Yates JR 3rd, Parker R, Hannon GJ (2005b) A role for the P-body component GW182 in microRNA function. Nat Cell Biol 7:1161–1166

    CAS  Google Scholar 

  • Liu Y, Mochizuki K, Gorovsky MA (2004b) Histone H3 lysine 9 methylation is required for DNA elimination in developing macronuclei in Tetrahymena. Proc Natl Acad Sci USA 101:1679–1684

    CAS  Google Scholar 

  • Llave C, Kasschau KD, Rector MA, Carrington JC (2002) Endogenous and silencing-associated small RNAs in plants. Plant Cell 14:1605–1619

    PubMed  CAS  Google Scholar 

  • Lynch M, Conery JS (2000) The evolutionary fate and consequences of duplicate genes. Science 290:1151–1155

    PubMed  CAS  Google Scholar 

  • Ma JB, Ye K, Patel DJ (2004) Structural basis for overhang-specific small interfering RNA recognition by the PAZ domain. Nature 429:318–322

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • MacRae IJ, Zhou K, Li F, Repic A, Brooks AN, Cande WZ, Adams PD, Doudna JA (2006) Structural basis for double-stranded RNA processing by Dicer. Science 311:195–198

    PubMed  CAS  Google Scholar 

  • Maine EM, Hauth J, Ratliff T, Vought VE, She X, Kelly WG (2005) EGO-1, a putative RNA-dependent RNA polymerase, is required for heterochromatin assembly on unpaired DNA during C. elegans meiosis. Curr Biol 15:1972–1978

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Martienssen RA, Zaratiegui M, Goto DB (2005) RNA interference and heterochromatin in the fission yeast Schizosaccharomyces pombe. Trends Genet 21:450–456

    PubMed  CAS  Google Scholar 

  • Matranga C, Tomari Y, Shin C, Bartel DP, Zamore PD (2005) Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes. Cell 123:607–620

    PubMed  CAS  Google Scholar 

  • Matzke MA, Birchler JA (2005) RNAi-mediated pathways in the nucleus. Nat Rev Genet 6:24–35

    PubMed  CAS  Google Scholar 

  • Medina M (2005) Genomes, phylogeny, and evolutionary systems biology. Proc Natl Acad Sci USA 102:6630–6635

    PubMed  CAS  Google Scholar 

  • Meister G, Tuschl T (2004) Mechanisms of gene silencing by double-stranded RNA. Nature 431:343–349

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Miki D, Shimamoto K (2004) Simple RNAi vectors for stable and transient suppression of gene function in rice. Plant Cell Physiol 45:490–495

    PubMed  CAS  Google Scholar 

  • Millar AA, Waterhouse PM (2005) Plant and animal microRNAs: similarities and differences. Funct Integr Genomics 5:129–135

    PubMed  CAS  Google Scholar 

  • Miyoshi K, Tsukumo H, Nagami T, Siomi H, Siomi MC (2005) Slicer function of Drosophila Argonautes and its involvement in RISC formation. Genes Dev 19:2837–2848

    PubMed  CAS  Google Scholar 

  • Mochizuki K., Gorovsky MA (2005) A dicer-like protein in Tetrahymena has distinct functions in genome rearrangement, chromosome segregation, and meiotic prophase. Genes Dev 19:77–89

    PubMed  CAS  Google Scholar 

  • Moore RC, Purugganan (2005) The evolutionary dynamics of plant duplicate genes. Curr Opin Plant Biol 8:122–128

    PubMed  CAS  Google Scholar 

  • Morris KV, Chan SW, Jacobsen SE, Looney DJ (2004) Small interfering RNA-induced transcriptional gene silencing in human cells. Science 305:1289–1292

    PubMed  CAS  Google Scholar 

  • Murchison EP, Partridge JF, Tam OH, Cheloufi S, Hannon GJ (2005) Characterization of Dicer-deficient murine embryonic stem cells. Proc Natl Acad Sci USA 102:12135–12140

    PubMed  CAS  Google Scholar 

  • Nakahara K, Kim K, Sciulli C, Dowd SR, Minden JS, Carthew RW (2005) Targets of microRNA regulation in the Drosophila oocyte proteome. Proc Natl Acad Sci USA 102:12023–12028

    PubMed  CAS  Google Scholar 

  • Nakayashiki H (2005) RNA silencing in fungi: mechanisms and applications. FEBS Lett 579:5950–5957

    PubMed  CAS  Google Scholar 

  • Nowacki M, Zagorski-Ostoja W, Meyer E (2005) Nowa1p and Nowa2p: Novel putative RNA binding proteins involved in trans-nuclear crosstalk in Paramecium tetraurelia. Curr Biol 15:1616–1628

    PubMed  CAS  Google Scholar 

  • Obbard DJ, Jiggins FM, Halligan DL, Little TJ (2006) Natural selection drives extremely rapid evolution in antiviral RNAi genes. Curr Biol 16:580–585

    PubMed  CAS  Google Scholar 

  • Ohno S (1970) Evolution by gene duplication. Springer, Berlin Heidelberg New York, pp 150

    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

    PubMed  CAS  Google Scholar 

  • Onodera Y, Haag JR, Ream T, Nunes PC, Pontes O, Pikaard CS (2005) Plant nuclear RNA polymerase IV mediates siRNA and DNA methylation-dependent heterochromatin formation. Cell 120:613–622

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Pal-Bhadra M, Leibovitch BA, Gandhi SG, Rao M, Bhadra U, Birchler JA, Elgin SC (2004) Heterochromatic silencing and HP1 localization in Drosophila are dependent on the RNAi machinery. Science 303:669–672

    PubMed  CAS  Google Scholar 

  • Pham JW, Pellino JL, Lee YS, Carthew RW, Sontheimer EJ (2004) A dicer-2-dependent 80S complex cleaves targeted mRNAs during RNAi in Drosophila. Cell 117:83–93

    PubMed  CAS  Google Scholar 

  • Philippe H, Lopez P, Brinkmann H, Budin K, Germot A, Lurent J, Moreira D, Muller M, Le Guyader H (2000) Early-branching or fast-evolving eukaryotes? An answer based on slowly evolving positions. Philos Trans R Soc Lond B Biol Sci 267:1213–1221

    CAS  Google Scholar 

  • Philippe H, Snell EA, Bapteste E, Lopez P, Holland PW, Casane D (2004) Phylogenomics of eukaryotes: impact of missing data on large alignments. Mol Biol Evol 21:1740–1752

    PubMed  CAS  Google Scholar 

  • Piccin A, Salameh A. Benna C, Sandrelli F, Mazzota G, Zordan M, Rosato E, Kyriacou CP, Costa R (2001) Efficient and heritable functional knock-out of an adult phenotype in Drosophila using a GAL4-driven hairpin RNA incorporating a heterologous spacer. Nucleic Acids Res 29:E55

    PubMed  CAS  Google Scholar 

  • Pillai RS, Bhattacharyya SN, Artus cG, Zoller T, Cougot N, Basyuk E, Bertrand E, Filipowicz W (2005) Inhibition of translation initiation by Let-7 microRNA in human cells. Science 309:1573–1576

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Ponger L, Li W-H (2005) Evolutionary diversification of DNA methyltransferases in eukaryotic genomes. Mol Biol Evol 22:1119–1128

    PubMed  CAS  Google Scholar 

  • Presgraves DC (2004) Evolutionary Genomics: new genes for new jobs. Curr Biol 15:R52–R53

    Google Scholar 

  • Qi Y, Denli AM, Hannon GJ (2005) Biochemical specialization within Arabidopsis RNA silencing pathways. Mol Cell 19:421–428

    PubMed  CAS  Google Scholar 

  • Ramesh MA, Malik S-B, Logsdon JM Jr (2005) A phylogenomic inventory of meiotic genes: evidence for sex in Giardia and an early eukaryotic origin of meiosis. Curr Biol 15:185–191

    PubMed  CAS  Google Scholar 

  • Rand TA, Petersen S, Du F, Wand X (2005) Argonaute2 cleaves the anti-guide strand of siRNA during RISC activation. Cell 123:621–629

    PubMed  CAS  Google Scholar 

  • Ray A, Lang JD, Golden T, Ray S (1996) SHORT INTEGUMENT (SIN1), a gene required for ovule development in Arabidopsis, also controls flowering time. Development 122:2631–2538

    PubMed  CAS  Google Scholar 

  • Rehwinkel J, Behm-Ansmant I, Gatfield D, Izaurralde E (2005) A crucial role for GW182 and the DCP1:DCP2 decapping complex in miRNA-mediated gene silencing. RNA 11:1640–1647

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Richards TA, Cavalier-Smith T (2005) Myosin domain evolution and the primary divergence of eukaryotes. Nature 436:1113–1118

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Robert VJ, Sijen T, van Wolfswinkel J, Plasterk RH (2005) Chromatin and RNAi factors protect the C. elegans germline against repetitive sequences. Genes Dev 19:782–787

    PubMed  CAS  Google Scholar 

  • Robinson KA, Beverley SM (2003) Improvements in transfection efficiency and tests of RNA interference (RNAi) approaches in the protozoan parasite Leishmania. Mol Biochem Parasitol 128:217–228

    PubMed  CAS  Google Scholar 

  • Rohr J, Sarkar N, Balenger S, Jeong B-R, Cerutti H (2004) Tandem inverted repeat system for selection of effective transgenic RNAi strains in Chlamydomonas. Plant J 40:611–621

    PubMed  CAS  Google Scholar 

  • Schroda M (2006) RNA silencing in Chlamydomonas: mechanisms and tools. Curr Genet 49:69–84

    PubMed  CAS  Google Scholar 

  • Schwab R, Palatnik JF, Riester M, Schommer C, Schmid M, Weigel D (2005) Specific effects of microRNAs on the plant transcriptome. Dev Cell 8:517–527

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Shi h, Djikeng A, Tschudi C, Ullu E (2004) Argonaute protein in the early divergent eukaryote Trypanosoma brucei: control of small interfering RNA accumulation and retroposon transcript abundance. Mol Cell Biol 24:420–427

    PubMed  Google Scholar 

  • Shiu PK, Raju NB, Zickler D, Metzenberg RL (2001) Meiotic silencing by unpaired DNA. Cell 107:905–916

    PubMed  CAS  Google Scholar 

  • Sigova A, Rhind N, Zamore PD (2004) A single Argonaute protein mediates both transcriptional and posttranscriptional silencing in Schizosaccharomyces pombe. Genes Dev 18:2359–2367

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Simpson AGB, Roger AJ (2004) The real ‘kingdoms’ of eukaryotes. Curr Biol 14:R693–R696

    PubMed  CAS  Google Scholar 

  • Smalheiser NR, Torvik VI (2005) Mammalian microRNAs derived from genomic repeats. Trends Genet 21:322–326

    PubMed  CAS  Google Scholar 

  • Sogin ML, Gunderson JH, Elwood HJ, Alonso RA, Peattie DA (1989) Phylogenetic meaning of the kingdom concept: an unusual ribosomal RNA from Giardia lamblia. Science 243:75–77

    PubMed  CAS  Google Scholar 

  • Sogin ML (1991) Early evolution and the origin of eukaryotes. Curr Opin Genet Dev 1:457–463

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Sontheimer EJ (2005) Assembly and function of RNA silencing complexes. Nat Rev Mol Cell Biol 6:127–138

    PubMed  CAS  Google Scholar 

  • Stechmann A, Cavalier-Smith T (2003) The root of the eukaryote tree pinpointed. Curr Biol 13:R665–R666

    PubMed  CAS  Google Scholar 

  • Stein P, Svoboda P, Anger M, Schultz RM (2003) RNAi: mammalian oocytes do it without RNA-dependent RNA polymerase. RNA 9:187–192

    PubMed  CAS  Google Scholar 

  • Sunkar R, Girke T, Zhu JK (2005) Identification and characterization of endogenous small interfering RNAs from rice. Nucleic Acids Res 33:4443–4454

    PubMed  CAS  Google Scholar 

  • Tang W, Samuels V, Whitley N, DeLaGarza T, Newton RJ (2004) Post-transcriptional gene silencing induced by short interfering RNAs in cultured transgenic plant cells. Genomic Proteomics Bioinformatics 2:97–108

    CAS  Google Scholar 

  • Ting AH, Schuebel KE, Herman JG, Baylin SB (2005) Short double-stranded RNA induces transcriptional gene silencing in human cancer cells in the absence of DNA methylation. Nat Genet 37:906–910

    PubMed  CAS  Google Scholar 

  • Tomari Y, Du T, Haley B, Schwarz DS, Bennett R, Cook HA, Koppetsch BS, Theurkauf WE, Zamore PD (2004) RISC assembly defects in the Drosophila RNAi mutant armitage. Cell 116:831–841

    PubMed  CAS  Google Scholar 

  • Tomari Y, Zamore PD (2005) Perspective: machines for RNAi. Genes Dev 19:517–529

    PubMed  CAS  Google Scholar 

  • Tran RK, Zilberman D, de Bustos C, Ditt RF, Henikoff JG, Lindroth AM, Delrow J, Boyle T, Kwong S, Bryson TD, Jacobsen SE, Henikoff S (2005) Chromatin and siRNA pathways cooperate to maintain DNA methylation of small transposable elements in Arabidopsis. Genome Biol 6:R90

    PubMed  Google Scholar 

  • Turner JM, Mahadevaiah SK, Fernandez-Capetillo O, Nussenzweig A, Xu X, Deng CX, Burgoyne PS (2005) Silencing of unsynapsed meiotic chromosomes in the mouse. Nat Genet 37:41–47

    PubMed  CAS  Google Scholar 

  • Ullu E, Tschudi C, Chakraborty T (2004) RNA interference in protozoan parasites. Cell Microbiol 6:509–519

    PubMed  CAS  Google Scholar 

  • Ullu E, Lujan HD, Tschudi C (2005) Small sense and antisense RNAs derived from a telomeric retroposon family in Giardia intestinalis. Eukaryot Cell 4:1155–1157

    PubMed  CAS  Google Scholar 

  • van Dijk K, Xu H, Cerutti H (2006) Epigenetic silencing of transposons in the green alga Chlamydomonas reinhardtii. In: Nellen W, Hammann C (eds) Small RNAs—analysis and regulatory functions. Springer, Berlin Heidelberg New York, pp 159–178

    Google Scholar 

  • Vayssie L, Vargas M, Weber C, Guillen N (2004) Double-stranded RNA mediates homology-dependent gene silencing of gamma-tubulin in the human parasite Entamoeba histolytica. Mol Biochem Parasitol 138:21–28

    PubMed  CAS  Google Scholar 

  • Verdel A, Jia S, Gerber S, Sugiyama T, Gygi S, Grewal SIS, Moazed D (2004) RNAi-mediated targeting of heterochromatin by the RITS complex. Science 303:672–676

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Wassenegger M, Krczal G (2006) Nomenclature and functions of RNA-directed RNA polymerases. Trends Plant Sci 11:142–151

    PubMed  CAS  Google Scholar 

  • Waterhouse PM, Wang MB, Lough T (2001) Gene silencing as an adaptive defence against viruses. Nature 411:834–842

    PubMed  CAS  Google Scholar 

  • Watson JM, Fusaro AF, Wang M, Waterhouse PM (2005) RNA silencing platforms in plants. FEBS Lett 579:5982–5987

    PubMed  CAS  Google Scholar 

  • Weinberg MS, Villeneuve LM, Ehsani A, Amarzguioui M, Aagaard L, Chen Z, Riggs AD, Rossi JJ, Morris KV (2006) The antisense strand of small interfering RNAs directs histone methylation and transcriptional gene silencing in human cells. RNA 12:256–262

    PubMed  CAS  Google Scholar 

  • Whisson SC, Avrova AO, van West P, Jones JT (2005) A method for double-stranded RNA-mediated transient gene silencing in Phytophthora infestans. Mol Plant Path 6:153–163

    CAS  Google Scholar 

  • Wong LH, Choo KHA (2004) Evolutionary dynamics of transposable elements at the centromere. Trends Genet 20:611–616

    PubMed  CAS  Google Scholar 

  • Wienholds E, Plasterk RHA (2005) MicroRNA function in animal development. FEBS Lett 579:5911–5922

    PubMed  CAS  Google Scholar 

  • Xie Z, Johansen LK, Gustafson AM, Kasschau KD, Lellis AD, Zilberman D, Jacobsen SE, Carrington JC (2004) Genetic and functional diversification of small RNA pathways in plants. PLoS Biol 2:E104

    PubMed  Google Scholar 

  • Xie Z, Allen E, Fahlgren N, Calamar A, Givan SA, Carrington JC (2005) Expression of Arabidopsis MIRNA genes. Plant Physiol 138:2145–2154

    PubMed  CAS  Google Scholar 

  • Yamada T, Fischle W, Sugiyama T, Allis CD, Grewal SI (2005) The nucleation and maintenance of heterochromatin by a histone deacetylase in fission yeast. Mol Cell 20:173–185

    PubMed  CAS  Google Scholar 

  • Yao MC, Chao JL (2005) RNA-guided DNA deletion in Tetrahymena: an RNAi-based mechanism for programmed genome rearrangements. Annu Rev Genet 39:537–559

    PubMed  CAS  Google Scholar 

  • Yoshikawa M, Peragine A, Park MY, Poethig RS (2005) A pathway for the biogenesis of trans-acting siRNAs in Arabidopsis. Genes Dev 19:2164–2175

    PubMed  CAS  Google Scholar 

  • Yu B, Yang Z, Li J, Minakhina S, Yang M, Padgett RW, Steward R, Chen X (2005) Methylation as a crucial step in plant microRNA biogenesis. Science 307:932–935

    PubMed  CAS  Google Scholar 

  • Yuan Y-R, Pei Y, Ma J-B, Kuryavyi V, Zhadina M, Meister G, Chen H-Y, Dauter Z, Tuschl T, Patel DJ (2005) Crystal structure of A. aeolicus argonaute, a site-specific DNA-guided endoribonuclease, provides insights into RISC-mediated mRNA cleavage. Mol Cell 19:405–419

    PubMed  CAS  Google Scholar 

  • Zamore PD, Haley B (2005) Ribo-gnome: the big world of small RNAs. Science 309:1519–1524

    PubMed  CAS  Google Scholar 

  • Zhang H, Kolb FA, Jaskiewicz L, Westhof E, Filipowicz W (2004) Single processing center models for human Dicer and bacterial RNaseIII. Cell 118:57–68

    PubMed  CAS  Google Scholar 

  • Zilberman D, Cao X, Jacobsen SE (2003) Argonaute4 control of locus-specific siRNA accumulation and DNA and histone methylation. Science 299:716–719

    PubMed  CAS  Google Scholar 

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Acknowledgments

We are grateful to members of the Cerutti lab for critical reading of the manuscript. This work was supported by a grant from the National Institutes of Health (GM62915).

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Correspondence to Heriberto Cerutti.

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Communicated by R. Bock

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Cerutti, H., Casas-Mollano, J.A. On the origin and functions of RNA-mediated silencing: from protists to man. Curr Genet 50, 81–99 (2006). https://doi.org/10.1007/s00294-006-0078-x

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