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PMID: 21427766 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

PIWI-interacting small RNAs: the vanguard of genome defence.

Nature reviews. Molecular cell biology ·Vol. 12 ·No. 4 ·2011-04-00 ·Pages 246-58

Siomi MC, Sato K, Pezic D, Aravin AA

Abstract

PIWI-interacting RNAs (piRNAs) are a distinct class of small non-coding RNAs that form the piRNA-induced silencing complex (piRISC) in the germ line of many animal species. The piRISC protects the integrity of the genome from invasion by 'genomic parasites'--transposable elements--by silencing them. Owing to their limited expression in gonads and their sequence diversity, piRNAs have been the most mysterious class of small non-coding RNAs regulating RNA silencing. Now, much progress is being made into our understanding of their biogenesis and molecular functions, including the specific subcellular compartmentalization of the piRNA pathway in granular cytoplasmic bodies.

MeSH Terms
Animals DNA Transposable Elements/genetics Genome/genetics Models, Genetic Mutagenesis, Insertional RNA Interference RNA, Small Interfering/genetics,metabolism RNA, Small Untranslated/genetics,metabolism
Chemicals
DNA Transposable Elements RNA, Small Interfering RNA, Small Untranslated
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Siomi Mikiko C
Keio University School of Medicine, Tokyo 160-8582, Japan. [email protected]
Sato Kaoru
Pezic Dubravka
Aravin Alexei A
References (100)
100 references, click to expand
  1. Biogenesis of small RNAs in animals.
    Nat Rev Mol Cell Biol. 2009 Feb;10(2):126-39 PMID: 19165215
  2. Genetic and molecular characterization of sting, a gene involved in crystal formation and meiotic drive in the male germ line of Drosophila melanogaster.
    Genetics. 1999 Feb;151(2):749-60 PMID: 9927466
  3. A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice.
    Mol Cell. 2008 Sep 26;31(6):785-99 PMID: 18922463
  4. How does the royal family of Tudor rule the PIWI-interacting RNA pathway?
    Genes Dev. 2010 Apr 1;24(7):636-46 PMID: 20360382
  5. Localization of mouse vasa homolog protein in chromatoid body and related nuage structures of mammalian spermatogenic cells during spermatogenesis.
    Histochem Cell Biol. 2010 Jun;133(6):627-39 PMID: 20401665
  6. Specialized piRNA pathways act in germline and somatic tissues of the Drosophila ovary.
    Cell. 2009 May 1;137(3):522-35 PMID: 19395010
  7. Unique germ-line organelle, nuage, functions to repress selfish genetic elements in Drosophila melanogaster.
    Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6714-9 PMID: 17428915
  8. Mouse MOV10L1 associates with Piwi proteins and is an essential component of the Piwi-interacting RNA (piRNA) pathway.
    Proc Natl Acad Sci U S A. 2010 Jun 29;107(26):11841-6 PMID: 20534472
  9. Expression and intracellular localization of mouse Vasa-homologue protein during germ cell development.
    Mech Dev. 2000 May;93(1-2):139-49 PMID: 10781947
  10. Developmentally regulated piRNA clusters implicate MILI in transposon control.
    Science. 2007 May 4;316(5825):744-7 PMID: 17446352
  11. HP1 recruitment in the absence of argonaute proteins in Drosophila.
    PLoS Genet. 2010 Mar 12;6(3):e1000880 PMID: 20300658
  12. Arginine methylation as a molecular signature of the Piwi small RNA pathway.
    Cell Cycle. 2009 Dec 15;8(24):4003-4 PMID: 19949292
  13. MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline.
    Dev Cell. 2007 Apr;12(4):503-14 PMID: 17395546
  14. GASZ is essential for male meiosis and suppression of retrotransposon expression in the male germline.
    PLoS Genet. 2009 Sep;5(9):e1000635 PMID: 19730684
  15. Localization of vasa protein to the Drosophila pole plasm is independent of its RNA-binding and helicase activities.
    Development. 1994 May;120(5):1201-11 PMID: 8026330
  16. MOV10L1 is necessary for protection of spermatocytes against retrotransposons by Piwi-interacting RNAs.
    Proc Natl Acad Sci U S A. 2010 Jun 29;107(26):11847-52 PMID: 20547853
  17. Maelstrom, a Drosophila spindle-class gene, encodes a protein that colocalizes with Vasa and RDE1/AGO1 homolog, Aubergine, in nuage.
    Development. 2003 Mar;130(5):859-71 PMID: 12538514
  18. Sorting of small RNAs into Arabidopsis argonaute complexes is directed by the 5' terminal nucleotide.
    Cell. 2008 Apr 4;133(1):116-27 PMID: 18342361
  19. COM, a heterochromatic locus governing the control of independent endogenous retroviruses from Drosophila melanogaster.
    Genetics. 2003 Jun;164(2):501-9 PMID: 12807771
  20. Valois, a component of the nuage and pole plasm, is involved in assembly of these structures, and binds to Tudor and the methyltransferase Capsuléen.
    Development. 2005 May;132(9):2167-77 PMID: 15800004
  21. Flamenco, a gene controlling the gypsy retrovirus of Drosophila melanogaster.
    Genetics. 1995 Feb;139(2):697-711 PMID: 7713426
  22. Structural basis for RNA unwinding by the DEAD-box protein Drosophila Vasa.
    Cell. 2006 Apr 21;125(2):287-300 PMID: 16630817
  23. A novel class of small RNAs bind to MILI protein in mouse testes.
    Nature. 2006 Jul 13;442(7099):203-7 PMID: 16751777
  24. Interplay of PIWI/Argonaute protein MIWI and kinesin KIF17b in chromatoid bodies of male germ cells.
    J Cell Sci. 2006 Jul 1;119(Pt 13):2819-25 PMID: 16787948
  25. A novel class of small RNAs in mouse spermatogenic cells.
    Genes Dev. 2006 Jul 1;20(13):1709-14 PMID: 16766680
  26. Arginine methylation of Piwi proteins catalysed by dPRMT5 is required for Ago3 and Aub stability.
    Nat Cell Biol. 2009 May;11(5):652-8 PMID: 19377467
  27. Gene silencing mechanisms mediated by Aubergine piRNA complexes in Drosophila male gonad.
    RNA. 2007 Nov;13(11):1911-22 PMID: 17872506
  28. Associations between PIWI proteins and TDRD1/MTR-1 are critical for integrated subcellular localization in murine male germ cells.
    Genes Cells. 2009 Oct;14(10):1155-65 PMID: 19735482
  29. Germ plasm and the differentiation of the germ cell line.
    Int Rev Cytol. 1975;43:229-80 PMID: 770367
  30. The small RNA profile during Drosophila melanogaster development.
    Dev Cell. 2003 Aug;5(2):337-50 PMID: 12919683
  31. Mouse Piwi interactome identifies binding mechanism of Tdrkh Tudor domain to arginine methylated Miwi.
    Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20336-41 PMID: 19918066
  32. The chromatoid body of male germ cells: similarity with processing bodies and presence of Dicer and microRNA pathway components.
    Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2647-52 PMID: 16477042
  33. Maternal mRNA deadenylation and decay by the piRNA pathway in the early Drosophila embryo.
    Nature. 2010 Oct 28;467(7319):1128-32 PMID: 20953170
  34. Argonaute protein PIWI controls mobilization of retrotransposons in the Drosophila male germline.
    Nucleic Acids Res. 2005 Apr 07;33(6):2052-9 PMID: 15817569
  35. Proteomic analysis of murine Piwi proteins reveals a role for arginine methylation in specifying interaction with Tudor family members.
    Genes Dev. 2009 Aug 1;23(15):1749-62 PMID: 19584108
  36. 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
  37. Small silencing RNAs: an expanding universe.
    Nat Rev Genet. 2009 Feb;10(2):94-108 PMID: 19148191
  38. Characterization of the piRNA complex from rat testes.
    Science. 2006 Jul 21;313(5785):363-7 PMID: 16778019
  39. A small-RNA perspective on gametogenesis, fertilization, and early zygotic development.
    Science. 2010 Oct 29;330(6004):617-22 PMID: 21030645
  40. The flamenco locus controls the gypsy and ZAM retroviruses and is required for Drosophila oogenesis.
    Genetics. 2007 Apr;175(4):1615-24 PMID: 17277359
  41. 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
  42. Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila.
    Cell. 2007 Mar 23;128(6):1089-103 PMID: 17346786
  43. The Yb protein defines a novel organelle and regulates male germline stem cell self-renewal in Drosophila melanogaster.
    J Cell Biol. 2009 May 18;185(4):613-27 PMID: 19433453
  44. Loss of the Mili-interacting Tudor domain-containing protein-1 activates transposons and alters the Mili-associated small RNA profile.
    Nat Struct Mol Biol. 2009 Jun;16(6):639-46 PMID: 19465913
  45. 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
  46. The Piwi-piRNA pathway provides an adaptive defense in the transposon arms race.
    Science. 2007 Nov 2;318(5851):761-4 PMID: 17975059
  47. The large Maf factor Traffic Jam controls gonad morphogenesis in Drosophila.
    Nat Cell Biol. 2003 Nov;5(11):994-1000 PMID: 14578908
  48. A regulatory circuit for piwi by the large Maf gene traffic jam in Drosophila.
    Nature. 2009 Oct 29;461(7268):1296-9 PMID: 19812547
  49. 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
  50. On the road to reading the RNA-interference code.
    Nature. 2009 Jan 22;457(7228):396-404 PMID: 19158785
  51. Collapse of germline piRNAs in the absence of Argonaute3 reveals somatic piRNAs in flies.
    Cell. 2009 May 1;137(3):509-21 PMID: 19395009
  52. In Drosophila melanogaster the COM locus directs the somatic silencing of two retrotransposons through both Piwi-dependent and -independent pathways.
    PLoS One. 2008 Feb 06;3(2):e1526 PMID: 18253480
  53. The RNA interference proteins and vasa locus are involved in the silencing of retrotransposons in the female germline of Drosophila melanogaster.
    RNA Biol. 2004 May;1(1):54-8 PMID: 17194939
  54. Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes.
    Nature. 2008 May 22;453(7194):534-8 PMID: 18404147
  55. Small RNAs as guardians of the genome.
    Cell. 2009 Feb 20;136(4):656-68 PMID: 19239887
  56. Repression of retroelements in Drosophila germline via piRNA pathway by the Tudor domain protein Tejas.
    Curr Biol. 2010 Apr 27;20(8):724-30 PMID: 20362446
  57. Cytoplasmic compartmentalization of the fetal piRNA pathway in mice.
    PLoS Genet. 2009 Dec;5(12):e1000764 PMID: 20011505
  58. 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
  59. Tdrd6 is required for spermiogenesis, chromatoid body architecture, and regulation of miRNA expression.
    Curr Biol. 2009 Apr 28;19(8):630-9 PMID: 19345099
  60. Mobile elements: drivers of genome evolution.
    Science. 2004 Mar 12;303(5664):1626-32 PMID: 15016989
  61. The biogenesis and function of PIWI proteins and piRNAs: progress and prospect.
    Annu Rev Cell Dev Biol. 2009;25:355-76 PMID: 19575643
  62. An in vivo RNAi assay identifies major genetic and cellular requirements for primary piRNA biogenesis in Drosophila.
    EMBO J. 2010 Oct 6;29(19):3301-17 PMID: 20818334
  63. A distinct small RNA pathway silences selfish genetic elements in the germline.
    Science. 2006 Jul 21;313(5785):320-4 PMID: 16809489
  64. Endogenous siRNAs derived from transposons and mRNAs in Drosophila somatic cells.
    Science. 2008 May 23;320(5879):1077-81 PMID: 18403677
  65. A broadly conserved pathway generates 3'UTR-directed primary piRNAs.
    Curr Biol. 2009 Dec 29;19(24):2066-76 PMID: 20022248
  66. An epigenetic activation role of Piwi and a Piwi-associated piRNA in Drosophila melanogaster.
    Nature. 2007 Nov 8;450(7167):304-8 PMID: 17952056
  67. Drosophila tudor is essential for polar granule assembly and pole cell specification, but not for posterior patterning.
    Genesis. 2004 Nov;40(3):164-70 PMID: 15495201
  68. The TDRD9-MIWI2 complex is essential for piRNA-mediated retrotransposon silencing in the mouse male germline.
    Dev Cell. 2009 Dec;17(6):775-87 PMID: 20059948
  69. Mouse maelstrom, a component of nuage, is essential for spermatogenesis and transposon repression in meiosis.
    Dev Cell. 2008 Aug;15(2):285-97 PMID: 18694567
  70. Structural basis for methylarginine-dependent recognition of Aubergine by Tudor.
    Genes Dev. 2010 Sep 1;24(17):1876-81 PMID: 20713507
  71. An epigenetic role for maternally inherited piRNAs in transposon silencing.
    Science. 2008 Nov 28;322(5906):1387-92 PMID: 19039138
  72. 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
  73. Probing the initiation and effector phases of the somatic piRNA pathway in Drosophila.
    Genes Dev. 2010 Nov 15;24(22):2499-504 PMID: 20966049
  74. Drosophila endogenous small RNAs bind to Argonaute 2 in somatic cells.
    Nature. 2008 Jun 5;453(7196):793-7 PMID: 18463636
  75. A slicer-mediated mechanism for repeat-associated siRNA 5' end formation in Drosophila.
    Science. 2007 Mar 16;315(5818):1587-90 PMID: 17322028
  76. tudor, a gene required for assembly of the germ plasm in Drosophila melanogaster.
    Cell. 1985 Nov;43(1):97-104 PMID: 3935320
  77. The Bombyx ovary-derived cell line endogenously expresses PIWI/PIWI-interacting RNA complexes.
    RNA. 2009 Jul;15(7):1258-64 PMID: 19460866
  78. MVH in piRNA processing and gene silencing of retrotransposons.
    Genes Dev. 2010 May;24(9):887-92 PMID: 20439430
  79. Small RNA-mediated quiescence of transposable elements in animals.
    Dev Cell. 2010 Nov 16;19(5):687-97 PMID: 21074719
  80. Mouse MAELSTROM: the link between meiotic silencing of unsynapsed chromatin and microRNA pathway?
    Hum Mol Genet. 2006 Aug 1;15(15):2324-34 PMID: 16787967
  81. Functional involvement of Tudor and dPRMT5 in the piRNA processing pathway in Drosophila germlines.
    EMBO J. 2009 Dec 16;28(24):3820-31 PMID: 19959991
  82. 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
  83. An ultrastructural study of primordial germ cells, oogonia and early oocytes in Xenopus laevis.
    J Embryol Exp Morphol. 1971 Oct;26(2):195-217 PMID: 5168216
  84. The Yb body, a major site for Piwi-associated RNA biogenesis and a gateway for Piwi expression and transport to the nucleus in somatic cells.
    J Biol Chem. 2011 Feb 4;286(5):3789-97 PMID: 21106531
  85. Zili is required for germ cell differentiation and meiosis in zebrafish.
    EMBO J. 2008 Oct 22;27(20):2702-11 PMID: 18833190
  86. Two mouse piwi-related genes: miwi and mili.
    Mech Dev. 2001 Oct;108(1-2):121-33 PMID: 11578866
  87. A germline-specific class of small RNAs binds mammalian Piwi proteins.
    Nature. 2006 Jul 13;442(7099):199-202 PMID: 16751776
  88. Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes.
    Nature. 2008 May 22;453(7194):539-43 PMID: 18404146
  89. 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
  90. The role of Tudor domains in germline development and polar granule architecture.
    Development. 2006 Oct;133(20):4053-62 PMID: 16971472
  91. Tudor and its domains: germ cell formation from a Tudor perspective.
    Cell Res. 2005 Apr;15(4):281-91 PMID: 15857583
  92. Heterochromatic silencing and HP1 localization in Drosophila are dependent on the RNAi machinery.
    Science. 2004 Jan 30;303(5658):669-72 PMID: 14752161
  93. Biogenesis pathways of piRNAs loaded onto AGO3 in the Drosophila testis.
    RNA. 2010 Dec;16(12):2503-15 PMID: 20980675
  94. DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes.
    Genes Dev. 2008 Apr 1;22(7):908-17 PMID: 18381894
  95. Mili interacts with tudor domain-containing protein 1 in regulating spermatogenesis.
    Curr Biol. 2009 Apr 28;19(8):640-4 PMID: 19345100
  96. Structural basis for recognition of arginine methylated Piwi proteins by the extended Tudor domain.
    Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18398-403 PMID: 20937909
  97. Roles for the Yb body components Armitage and Yb in primary piRNA biogenesis in Drosophila.
    Genes Dev. 2010 Nov 15;24(22):2493-8 PMID: 20966047
  98. Transplantation of posterior polar plasm in Drosophila. Induction of germ cells at the anterior pole of the egg.
    Proc Natl Acad Sci U S A. 1974 Apr;71(4):1016-20 PMID: 4208545
  99. The Drosophila HP1 homolog Rhino is required for transposon silencing and piRNA production by dual-strand clusters.
    Cell. 2009 Sep 18;138(6):1137-49 PMID: 19732946
  100. Drosophila PIWI associates with chromatin and interacts directly with HP1a.
    Genes Dev. 2007 Sep 15;21(18):2300-11 PMID: 17875665
Article Info
Journal
Nature reviews. Molecular cell biology
Abbr.
Nat Rev Mol Cell Biol
ISSN
1471-0080
DOI
10.1038/nrm3089
Email
[email protected]
Published
2011-04-00
Pages
246-58
Language
English
Region
England
NLM ID
100962782
Subset
IM
Grants
NIH HHS · DP2 OD007371A · United States
NICHD NIH HHS · R00 HD057233‑02 · United States
External Links
PubMed source DOI: 10.1038/nrm3089 View journal details
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