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PMID: 18571451 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Piwi and piRNAs act upstream of an endogenous siRNA pathway to suppress Tc3 transposon mobility in the Caenorhabditis elegans germline.

Molecular cell ·Vol. 31 ·No. 1 ·2008-07-11 ·Pages 79-90

Das PP, Bagijn MP, Goldstein LD, Woolford JR, Lehrbach NJ, Sapetschnig A, Buhecha HR, Gilchrist MJ, Howe KL, Stark R, Matthews N, Berezikov E, Ketting RF, Tavaré S, Miska EA

Abstract

The Piwi proteins of the Argonaute superfamily are required for normal germline development in Drosophila, zebrafish, and mice and associate with 24-30 nucleotide RNAs termed piRNAs. We identify a class of 21 nucleotide RNAs, previously named 21U-RNAs, as the piRNAs of C. elegans. Piwi and piRNA expression is restricted to the male and female germline and independent of many proteins in other small-RNA pathways, including DCR-1. We show that Piwi is specifically required to silence Tc3, but not other Tc/mariner DNA transposons. Tc3 excision rates in the germline are increased at least 100-fold in piwi mutants as compared to wild-type. We find no evidence for a Ping-Pong model for piRNA amplification in C. elegans. Instead, we demonstrate that Piwi acts upstream of an endogenous siRNA pathway in Tc3 silencing. These data might suggest a link between piRNA and siRNA function.

MeSH Terms
Animals Argonaute Proteins Caenorhabditis elegans/genetics,metabolism Caenorhabditis elegans Proteins/metabolism DNA Transposable Elements/genetics Drosophila Proteins Female Gene Silencing Genes, Helminth Germ Cells/growth & development,metabolism Male Proteins/genetics,metabolism RNA, Helminth/metabolism RNA, Small Interfering/metabolism RNA-Induced Silencing Complex Transposases/metabolism
Chemicals
Argonaute Proteins Caenorhabditis elegans Proteins DNA Transposable Elements Drosophila Proteins PRG-1 protein, C elegans PRG-2 protein, C elegans Proteins RNA, Helminth RNA, Small Interfering RNA-Induced Silencing Complex piwi protein, Drosophila Transposases
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Das Partha P
Wellcome Trust Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK.
Bagijn Marloes P
Goldstein Leonard D
Woolford Julie R
Lehrbach Nicolas J
Sapetschnig Alexandra
Buhecha Heeran R
Gilchrist Michael J
Howe Kevin L
Stark Rory
Matthews Nik
Berezikov Eugene
Ketting René F
Tavaré Simon
Miska Eric A
References (73)
73 references, click to expand
  1. The microRNAs of Caenorhabditis elegans.
    Genes Dev. 2003 Apr 15;17(8):991-1008 PMID: 12672692
  2. Functional genomic analysis of C. elegans chromosome I by systematic RNA interference.
    Nature. 2000 Nov 16;408(6810):325-30 PMID: 11099033
  3. COM, a heterochromatic locus governing the control of independent endogenous retroviruses from Drosophila melanogaster.
    Genetics. 2003 Jun;164(2):501-9 PMID: 12807771
  4. Endogenous siRNAs derived from transposons and mRNAs in Drosophila somatic cells.
    Science. 2008 May 23;320(5879):1077-81 PMID: 18403677
  5. A novel class of evolutionarily conserved genes defined by piwi are essential for stem cell self-renewal.
    Genes Dev. 1998 Dec 1;12(23):3715-27 PMID: 9851978
  6. Characterization of a germ-line proliferation mutation in C. elegans.
    Development. 1992 Nov;116(3):755-66 PMID: 1289064
  7. Loss of the putative RNA-directed RNA polymerase RRF-3 makes C. elegans hypersensitive to RNAi.
    Curr Biol. 2002 Aug 6;12(15):1317-9 PMID: 12176360
  8. Mobilization of quiet, endogenous Tc3 transposons of Caenorhabditis elegans by forced expression of Tc3 transposase.
    EMBO J. 1993 Jun;12(6):2513-20 PMID: 8389698
  9. Cutoff and aubergine mutations result in retrotransposon upregulation and checkpoint activation in Drosophila.
    Curr Biol. 2007 Apr 3;17(7):637-42 PMID: 17363252
  10. MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline.
    Dev Cell. 2007 Apr;12(4):503-14 PMID: 17395546
  11. Molecular biology. Amplified silencing.
    Science. 2007 Jan 12;315(5809):199-200 PMID: 17218517
  12. SMEDWI-2 is a PIWI-like protein that regulates planarian stem cells.
    Science. 2005 Nov 25;310(5752):1327-30 PMID: 16311336
  13. An extensive class of small RNAs in Caenorhabditis elegans.
    Science. 2001 Oct 26;294(5543):862-4 PMID: 11679672
  14. Functional genomic analysis of RNA interference in C. elegans.
    Science. 2005 May 20;308(5725):1164-7 PMID: 15790806
  15. Methylation protects miRNAs and siRNAs from a 3'-end uridylation activity in Arabidopsis.
    Curr Biol. 2005 Aug 23;15(16):1501-7 PMID: 16111943
  16. MicroRNAs and other tiny endogenous RNAs in C. elegans.
    Curr Biol. 2003 May 13;13(10):807-18 PMID: 12747828
  17. Flamenco, a gene controlling the gypsy retrovirus of Drosophila melanogaster.
    Genetics. 1995 Feb;139(2):697-711 PMID: 7713426
  18. A role for the RNase III enzyme DCR-1 in RNA interference and germ line development in Caenorhabditis elegans.
    Science. 2001 Sep 21;293(5538):2269-71 PMID: 11486053
  19. Large-scale sequencing reveals 21U-RNAs and additional microRNAs and endogenous siRNAs in C. elegans.
    Cell. 2006 Dec 15;127(6):1193-207 PMID: 17174894
  20. EGO-1 is related to RNA-directed RNA polymerase and functions in germ-line development and RNA interference in C. elegans.
    Curr Biol. 2000 Feb 24;10(4):169-78 PMID: 10704412
  21. A novel class of small RNAs bind to MILI protein in mouse testes.
    Nature. 2006 Jul 13;442(7099):203-7 PMID: 16751777
  22. A novel class of small RNAs in mouse spermatogenic cells.
    Genes Dev. 2006 Jul 1;20(13):1709-14 PMID: 16766680
  23. Transposon silencing in the Caenorhabditis elegans germ line by natural RNAi.
    Nature. 2003 Nov 20;426(6964):310-4 PMID: 14628056
  24. Specific association of Piwi with rasiRNAs derived from retrotransposon and heterochromatic regions in the Drosophila genome.
    Genes Dev. 2006 Aug 15;20(16):2214-22 PMID: 16882972
  25. Characterization of the piRNA complex from rat testes.
    Science. 2006 Jul 21;313(5785):363-7 PMID: 16778019
  26. The Argonaute family: tentacles that reach into RNAi, developmental control, stem cell maintenance, and tumorigenesis.
    Genes Dev. 2002 Nov 1;16(21):2733-42 PMID: 12414724
  27. Pimet, the Drosophila homolog of HEN1, mediates 2'-O-methylation of Piwi- interacting RNAs at their 3' ends.
    Genes Dev. 2007 Jul 1;21(13):1603-8 PMID: 17606638
  28. Biogenesis and germline functions of piRNAs.
    Development. 2008 Jan;135(1):3-9 PMID: 18032451
  29. piwi encodes a nucleoplasmic factor whose activity modulates the number and division rate of germline stem cells.
    Development. 2000 Feb;127(3):503-14 PMID: 10631171
  30. Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila.
    Cell. 2007 Mar 23;128(6):1089-103 PMID: 17346786
  31. Characterization of the Caenorhabditis elegans Tc1 transposase in vivo and in vitro.
    Genes Dev. 1993 Jul;7(7A):1244-53 PMID: 8391505
  32. Mut-7 of C. elegans, required for transposon silencing and RNA interference, is a homolog of Werner syndrome helicase and RNaseD.
    Cell. 1999 Oct 15;99(2):133-41 PMID: 10535732
  33. PRG-1 and 21U-RNAs interact to form the piRNA complex required for fertility in C. elegans.
    Mol Cell. 2008 Jul 11;31(1):67-78 PMID: 18571452
  34. The Drosophila RNA methyltransferase, DmHen1, modifies germline piRNAs and single-stranded siRNAs in RISC.
    Curr Biol. 2007 Jul 17;17(14):1265-72 PMID: 17604629
  35. The rde-1 gene, RNA interference, and transposon silencing in C. elegans.
    Cell. 1999 Oct 15;99(2):123-32 PMID: 10535731
  36. Systematic functional analysis of the Caenorhabditis elegans genome using RNAi.
    Nature. 2003 Jan 16;421(6920):231-7 PMID: 12529635
  37. Double-stranded RNA-mediated silencing of genomic tandem repeats and transposable elements in the D. melanogaster germline.
    Curr Biol. 2001 Jul 10;11(13):1017-27 PMID: 11470406
  38. Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing.
    Cell. 2001 Jul 13;106(1):23-34 PMID: 11461699
  39. Genetic analysis of Caenorhabditis elegans glp-1 mutants suggests receptor interaction or competition.
    Genetics. 2003 Jan;163(1):115-32 PMID: 12586701
  40. Telomere elongation is under the control of the RNAi-based mechanism in the Drosophila germline.
    Genes Dev. 2006 Feb 1;20(3):345-54 PMID: 16452506
  41. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans.
    Science. 2001 Oct 26;294(5543):858-62 PMID: 11679671
  42. The mechanism of transposition of Tc3 in C. elegans.
    Cell. 1994 Oct 21;79(2):293-301 PMID: 7954797
  43. Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes.
    Nature. 2008 May 22;453(7194):534-8 PMID: 18404147
  44. Drosophila rasiRNA pathway mutations disrupt embryonic axis specification through activation of an ATR/Chk2 DNA damage response.
    Dev Cell. 2007 Jan;12(1):45-55 PMID: 17199040
  45. Secondary siRNAs result from unprimed RNA synthesis and form a distinct class.
    Science. 2007 Jan 12;315(5809):244-7 PMID: 17158288
  46. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans.
    Nature. 1998 Feb 19;391(6669):806-11 PMID: 9486653
  47. A distinct small RNA pathway silences selfish genetic elements in the germline.
    Science. 2006 Jul 21;313(5785):320-4 PMID: 16809489
  48. The Argonautes.
    Cold Spring Harb Symp Quant Biol. 2006;71:67-72 PMID: 17381282
  49. miwi, a murine homolog of piwi, encodes a cytoplasmic protein essential for spermatogenesis.
    Dev Cell. 2002 Jun;2(6):819-30 PMID: 12062093
  50. Spontaneous unstable unc-22 IV mutations in C. elegans var. Bergerac.
    Genetics. 1984 Dec;108(4):859-77 PMID: 6096205
  51. Ingestion of bacterially expressed dsRNAs can produce specific and potent genetic interference in Caenorhabditis elegans.
    Gene. 2001 Jan 24;263(1-2):103-12 PMID: 11223248
  52. Analysis of the C. elegans Argonaute family reveals that distinct Argonautes act sequentially during RNAi.
    Cell. 2006 Nov 17;127(4):747-57 PMID: 17110334
  53. A C. elegans Piwi, PRG-1, regulates 21U-RNAs during spermatogenesis.
    Curr Biol. 2008 Jun 24;18(12):861-7 PMID: 18501605
  54. A role for Piwi and piRNAs in germ cell maintenance and transposon silencing in Zebrafish.
    Cell. 2007 Apr 6;129(1):69-82 PMID: 17418787
  55. Genome sequence of the nematode C. elegans: a platform for investigating biology.
    Science. 1998 Dec 11;282(5396):2012-8 PMID: 9851916
  56. Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans.
    Genes Dev. 2001 Oct 15;15(20):2654-9 PMID: 11641272
  57. A slicer-mediated mechanism for repeat-associated siRNA 5' end formation in Drosophila.
    Science. 2007 Mar 16;315(5818):1587-90 PMID: 17322028
  58. Gain-of-function mutations of fem-3, a sex-determination gene in Caenorhabditis elegans.
    Genetics. 1987 Jan;115(1):107-19 PMID: 3557107
  59. The 3' termini of mouse Piwi-interacting RNAs are 2'-O-methylated.
    Nat Struct Mol Biol. 2007 Apr;14(4):349-50 PMID: 17384646
  60. Distinct populations of primary and secondary effectors during RNAi in C. elegans.
    Science. 2007 Jan 12;315(5809):241-4 PMID: 17124291
  61. Analysis of a piwi-related gene implicates small RNAs in genome rearrangement in tetrahymena.
    Cell. 2002 Sep 20;110(6):689-99 PMID: 12297043
  62. Mili, a mammalian member of piwi family gene, is essential for spermatogenesis.
    Development. 2004 Feb;131(4):839-49 PMID: 14736746
  63. Intersex, a temperature-sensitive mutant of the nematode Caenorhabditis elegans.
    Dev Biol. 1978 Oct;66(2):386-409 PMID: 700253
  64. A novel group of pumilio mutations affects the asymmetric division of germline stem cells in the Drosophila ovary.
    Development. 1997 Jun;124(12):2463-76 PMID: 9199372
  65. Two mouse piwi-related genes: miwi and mili.
    Mech Dev. 2001 Oct;108(1-2):121-33 PMID: 11578866
  66. Domains in gene silencing and cell differentiation proteins: the novel PAZ domain and redefinition of the Piwi domain.
    Trends Biochem Sci. 2000 Oct;25(10):481-2 PMID: 11050429
  67. A germline-specific class of small RNAs binds mammalian Piwi proteins.
    Nature. 2006 Jul 13;442(7099):199-202 PMID: 16751776
  68. Mouse Piwi-interacting RNAs are 2'-O-methylated at their 3' termini.
    Nat Struct Mol Biol. 2007 Apr;14(4):347-8 PMID: 17384647
  69. MicroRNAs: genomics, biogenesis, mechanism, and function.
    Cell. 2004 Jan 23;116(2):281-97 PMID: 14744438
  70. Specification of male development in Caenorhabditis elegans: the fem genes.
    Dev Biol. 1984 Sep;105(1):234-9 PMID: 6468762
  71. Identification and characterization of two novel classes of small RNAs in the mouse germline: retrotransposon-derived siRNAs in oocytes and germline small RNAs in testes.
    Genes Dev. 2006 Jul 1;20(13):1732-43 PMID: 16766679
  72. Transposase is the only nematode protein required for in vitro transposition of Tc1.
    Genes Dev. 1996 Mar 15;10(6):755-61 PMID: 8598301
  73. zucchini and squash encode two putative nucleases required for rasiRNA production in the Drosophila germline.
    Dev Cell. 2007 Jun;12(6):851-62 PMID: 17543859
Article Info
Journal
Molecular cell
Abbr.
Mol Cell
ISSN
1097-4164
DOI
10.1016/j.molcel.2008.06.003
Published
2008-07-11
Epub
2008-00-19
Pages
79-90
Language
English
Region
United States
NLM ID
9802571
PMCID
PMC3353317
Subset
IM
Grants
Wellcome Trust · 092096 · United Kingdom
Medical Research Council · United Kingdom
Cancer Research UK · C13474 · United Kingdom
External Links
PubMed source DOI: 10.1016/j.molcel.2008.06.003 PMC Full Text View journal details
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