1932

Abstract

PIWI-interacting RNAs (piRNAs) and their associated PIWI clade Argonaute proteins constitute the core of the piRNA pathway. In gonadal cells, this conserved pathway is crucial for genome defense, and its main function is to silence transposable elements. This is achieved through posttranscriptional and transcriptional gene silencing. Precursors that give rise to piRNAs require specialized transcription and transport machineries because piRNA biogenesis is a cytoplasmic process. The ping-pong cycle, a posttranscriptional silencing mechanism, combines the cleavage-dependent silencing of transposon RNAs with piRNA production. PIWI proteins also function in the nucleus, where they scan for nascent target transcripts with sequence complementarity, instructing transcriptional silencing and deposition of repressive chromatin marks at transposon loci. Although studies have revealed numerous factors that participate in each branch of the piRNA pathway, the precise molecular roles of these factors often remain unclear. In this review, we summarize our current understanding of the mechanisms involved in piRNA biogenesis and function.

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2018-11-23
2024-03-28
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Literature Cited

  1. 1.  Akay A, Di Domenico T, Suen KM, Nabih A, Parada GE et al. 2017. The helicase Aquarius/EMB-4 is required to overcome intronic barriers to allow nuclear RNAi pathways to heritably silence transcription. Dev. Cell 42:241–55.e6
    [Google Scholar]
  2. 2.  Akkouche A, Mugat B, Barckmann B, Varela-Chavez C, Li B et al. 2017. Piwi is required during Drosophila embryogenesis to license dual-strand piRNA clusters for transposon repression in adult ovaries. Mol. Cell 66:411–19.e4
    [Google Scholar]
  3. 3.  Andersen PR, Tirian L, Vunjak M, Brennecke J 2017. A heterochromatin-dependent transcription machinery drives piRNA expression. Nature 549:54–59
    [Google Scholar]
  4. 4.  Aravin A, Gaidatzis D, Pfeffer S, Lagos-Quintana M, Landgraf P et al. 2006. A novel class of small RNAs bind to MILI protein in mouse testes. Nature 442:203–207
    [Google Scholar]
  5. 5.  Aravin AA, Lagos-Quintana M, Yalcin A, Zavolan M, Marks D et al. 2003. The small RNA profile during Drosophila melanogaster development. Dev. Cell 5:337–50
    [Google Scholar]
  6. 6.  Aravin AA, Naumova NM, Tulin AV, Vagin VV, Rozovsky YM, Gvozdev VA 2001. Double-stranded RNA-mediated silencing of genomic tandem repeats and transposable elements in the D. melanogaster germline. Curr. Biol. 11:1017–27
    [Google Scholar]
  7. 7.  Aravin AA, Sachidanandam R, Bourc'his D, Schaefer C, Pezic D et al. 2008. A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice. Mol. Cell 31:785–99
    [Google Scholar]
  8. 8.  Aravin AA, Sachidanandam R, Girard A, Fejes-Toth K, Hannon GJ 2007. Developmentally regulated piRNA clusters implicate MILI in transposon control. Science 316:744–47
    [Google Scholar]
  9. 9.  Ashe A, Sapetschnig A, Weick E-M, Mitchell J, Bagijn MP et al. 2012. piRNAs can trigger a multigenerational epigenetic memory in the germline of C. elegans. Cell 150:88–99
    [Google Scholar]
  10. 10.  Brennecke J, Aravin AA, Stark A, Dus M, Kellis M et al. 2007. Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila. Cell 128:1089–103
    [Google Scholar]
  11. 11.  Brennecke J, Malone CD, Aravin AA, Sachidanandam R, Stark A, Hannon GJ 2008. An epigenetic role for maternally inherited piRNAs in transposon silencing. Science 322:1387–92
    [Google Scholar]
  12. 12.  Brower-Toland B, Findley SD, Jiang L, Liu L, Yin H et al. 2007. Drosophila PIWI associates with chromatin and interacts directly with HP1a. Genes Dev 21:2300–11
    [Google Scholar]
  13. 13.  Bucheton A, Paro R, Sang HM, Pelisson A, Finnegan DJ 1984. The molecular basis of I-R hybrid dysgenesis in Drosophila melanogaster: identification, cloning, and properties of the I factor. Cell 38:153–63
    [Google Scholar]
  14. 14.  Buckley BA, Burkhart KB, Gu SG, Spracklin G, Kershner A et al. 2012. A nuclear Argonaute promotes multigenerational epigenetic inheritance and germline immortality. Nature 489:447–51
    [Google Scholar]
  15. 15.  Bühler M, Verdel A, Moazed D 2006. Tethering RITS to a nascent transcript initiates RNAi- and heterochromatin-dependent gene silencing. Cell 125:873–86
    [Google Scholar]
  16. 16.  Cecere G, Zheng GX, Mansisidor AR, Klymko KE, Grishok A 2012. Promoters recognized by Forkhead proteins exist for individual 21U-RNAs. Mol. Cell 47:734–45
    [Google Scholar]
  17. 17.  Chen K-M, Campbell E, Pandey RR, Yang Z, McCarthy AA, Pillai RS 2015. Metazoan Maelstrom is an RNA-binding protein that has evolved from an ancient nuclease active in protists. RNA 21:833–39
    [Google Scholar]
  18. 18.  Chen Y-CA, Stuwe E, Luo Y, Ninova M, Le Thomas A et al. 2016. Cutoff suppresses RNA polymerase II termination to ensure expression of piRNA precursors. Mol. Cell 63:97–109
    [Google Scholar]
  19. 19.  Clark JP, Rahman R, Yang N, Yang LH, Lau NC 2017. Drosophila PAF1 modulates PIWI/piRNA silencing capacity. Curr. Biol. 27:2718–26.e4
    [Google Scholar]
  20. 20.  Colmenares SU, Buker SM, Buhler M, Dlakić M, Moazed D 2007. Coupling of double-stranded RNA synthesis and siRNA generation in fission yeast RNAi. Mol. Cell 27:449–61
    [Google Scholar]
  21. 21.  Cora E, Pandey RR, Xiol J, Taylor J, Sachidanandam R et al. 2014. The MID-PIWI module of Piwi proteins specifies nucleotide- and strand-biases of piRNAs. RNA 20:773–81
    [Google Scholar]
  22. 22.  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 12:3715–27
    [Google Scholar]
  23. 23.  Czech B, Preall JB, McGinn J, Hannon GJ 2013. A transcriptome-wide RNAi screen in the Drosophila ovary reveals factors of the germline piRNA pathway. Mol. Cell 50:749–61
    [Google Scholar]
  24. 24.  Das PP, Bagijn MP, Goldstein LD, Woolford JR, Lehrbach NJ et al. 2008. Piwi and piRNAs act upstream of an endogenous siRNA pathway to suppress Tc3 transposon mobility in the Caenorhabditis elegans germline. Mol. Cell 31:79–90
    [Google Scholar]
  25. 25.  De Fazio S, Bartonicek N, Di Giacomo M, Abreu-Goodger C, Sankar A et al. 2011. The endonuclease activity of Mili fuels piRNA amplification that silences LINE1 elements. Nature 480:259–63
    [Google Scholar]
  26. 26.  de Vanssay A, Bouge AL, Boivin A, Hermant C, Teysset L et al. 2012. Paramutation in Drosophila linked to emergence of a piRNA-producing locus. Nature 490:112–15
    [Google Scholar]
  27. 27.  Dennis C, Brasset E, Sarkar A, Vaury C 2016. Export of piRNA precursors by EJC triggers assembly of cytoplasmic Yb-body in Drosophila. Nat. Commun. 7:13739
    [Google Scholar]
  28. 28.  Dennis C, Zanni V, Brasset E, Eymery A, Zhang L et al. 2013. “Dot COM”, a nuclear transit center for the primary piRNA pathway in Drosophila. PLOS ONE 8:e72752
    [Google Scholar]
  29. 29.  Ding D, Liu J, Dong K, Midic U, Hess RA et al. 2017. PNLDC1 is essential for piRNA 3′ end trimming and transposon silencing during spermatogenesis in mice. Nat. Commun. 8:819
    [Google Scholar]
  30. 30.  Dönertas D, Sienski G, Brennecke J 2013. Drosophila Gtsf1 is an essential component of the Piwi-mediated transcriptional silencing complex. Genes Dev 27:1693–705
    [Google Scholar]
  31. 31.  Fagegaltier D, Falciatori I, Czech B, Castel S, Perrimon N et al. 2016. Oncogenic transformation of Drosophila somatic cells induces a functional piRNA pathway. Genes Dev 30:1623–35
    [Google Scholar]
  32. 32.  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 130:859–71
    [Google Scholar]
  33. 33.  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 391:806–11
    [Google Scholar]
  34. 33a.  Gainetdinov I, Colpan C, Arif A, Cecchini K, Zamore PD 2018. A single mechanism of biogenesis, initiated and directed by PIWI proteins, explains piRNA production in most animals. Mol. Cell 71:775–90
    [Google Scholar]
  35. 34.  Gerace EL, Halic M, Moazed D 2010. The methyltransferase activity of Clr4Suv39h triggers RNAi independently of histone H3K9 methylation. Mol. Cell 39:360–72
    [Google Scholar]
  36. 35.  Girard A, Sachidanandam R, Hannon GJ, Carmell MA 2006. A germline-specific class of small RNAs binds mammalian Piwi proteins. Nature 442:199–202
    [Google Scholar]
  37. 36.  Goh W-SS, Seah JWE, Harrison EJ, Chen C, Hammell CM, Hannon GJ 2014. A genome-wide RNAi screen identifies factors required for distinct stages of C. elegans piRNA biogenesis. Genes Dev 28:797–807
    [Google Scholar]
  38. 37.  Goriaux C, Desset S, Renaud Y, Vaury C, Brasset E 2014. Transcriptional properties and splicing of the flamenco piRNA cluster. EMBO Rep 15:411–18
    [Google Scholar]
  39. 38.  Grimson A, Srivastava M, Fahey B, Woodcroft BJ, Chiang HR et al. 2008. Early origins and evolution of microRNAs and Piwi-interacting RNAs in animals. Nature 455:1193–97
    [Google Scholar]
  40. 39.  Grivna ST, Beyret E, Wang Z, Lin H 2006. A novel class of small RNAs in mouse spermatogenic cells. Genes Dev 20:1709–14
    [Google Scholar]
  41. 40.  Gu W, Lee H-C, Chaves D, Youngman EM, Pazour GJ et al. 2012. CapSeq and CIP-TAP identify Pol II start sites and reveal capped small RNAs as C. elegans piRNA precursors. Cell 151:1488–500
    [Google Scholar]
  42. 41.  Gunawardane LS, Saito K, Nishida KM, Miyoshi K, Kawamura Y et al. 2007. A Slicer-mediated mechanism for repeat-associated siRNA 5′ end formation in Drosophila. Science 315:1587–90
    [Google Scholar]
  43. 42.  Haase AD, Fenoglio S, Muerdter F, Guzzardo PM, Czech B et al. 2010. Probing the initiation and effector phases of the somatic piRNA pathway in Drosophila. Genes Dev 24:2499–504
    [Google Scholar]
  44. 43.  Han BW, Wang W, Li C, Weng Z, Zamore PD 2015. piRNA-guided transposon cleavage initiates Zucchini-dependent, phased piRNA production. Science 348:817–21
    [Google Scholar]
  45. 44.  Handler D, Meixner K, Pizka M, Lauss K, Schmied C et al. 2013. The genetic makeup of the Drosophila piRNA pathway. Mol. Cell 50:762–77
    [Google Scholar]
  46. 45.  Handler D, Olivieri D, Novatchkova M, Gruber FS, Meixner K et al. 2011. A systematic analysis of Drosophila TUDOR domain-containing proteins identifies Vreteno and the Tdrd12 family as essential primary piRNA pathway factors. EMBO J 30:3977–93
    [Google Scholar]
  47. 46.  Harris AN, Macdonald PM 2001. aubergine encodes a Drosophila polar granule component required for pole cell formation and related to eIF2C. Development 128:2823–32
    [Google Scholar]
  48. 47.  Hayashi R, Schnabl J, Handler D, Mohn F, Ameres SL, Brennecke J 2016. Genetic and mechanistic diversity of piRNA 3′-end formation. Nature 539:588–92
    [Google Scholar]
  49. 48.  Heard E, Martienssen RA 2014. Transgenerational epigenetic inheritance: myths and mechanisms. Cell 157:95–109
    [Google Scholar]
  50. 49.  Hermant C, Boivin A, Teysset L, Delmarre V, Asif-Laidin A et al. 2015. Paramutation in Drosophila requires both nuclear and cytoplasmic actors of the piRNA pathway and induces cis-spreading of piRNA production. Genetics 201:1381–96
    [Google Scholar]
  51. 50.  Herr AJ, Jensen MB, Dalmay T, Baulcombe DC 2005. RNA polymerase IV directs silencing of endogenous DNA. Science 308:118–20
    [Google Scholar]
  52. 51.  Homolka D, Pandey RR, Goriaux C, Brasset E, Vaury C et al. 2015. PIWI slicing and RNA elements in precursors instruct directional primary piRNA biogenesis. Cell Rep 12:418–28
    [Google Scholar]
  53. 52.  Honda S, Kirino Y, Maragkakis M, Alexiou P, Ohtaki A et al. 2013. Mitochondrial protein BmPAPI modulates the length of mature piRNAs. RNA 19:1405–18
    [Google Scholar]
  54. 53.  Horwich MD, Li C, Matranga C, Vagin V, Farley G et al. 2007. The Drosophila RNA methyltransferase, DmHen1, modifies germline piRNAs and single-stranded siRNAs in RISC. Curr. Biol. 17:1265–72
    [Google Scholar]
  55. 54.  Houwing S, Kamminga LM, Berezikov E, Cronembold D, Girard A et al. 2007. A role for Piwi and piRNAs in germ cell maintenance and transposon silencing in zebrafish. Cell 129:69–82
    [Google Scholar]
  56. 55.  Hur JK, Luo Y, Moon S, Ninova M, Marinov GK et al. 2016. Splicing-independent loading of TREX on nascent RNA is required for efficient expression of dual-strand piRNA clusters in Drosophila. Genes Dev 30:840–55
    [Google Scholar]
  57. 56.  Hutvagner G, Simard MJ 2008. Argonaute proteins: key players in RNA silencing. Nat. Rev. Mol. Cell Biol. 9:22–32
    [Google Scholar]
  58. 57.  Ipsaro JJ, Haase AD, Knott SR, Joshua-Tor L, Hannon GJ 2012. The structural biochemistry of Zucchini implicates it as a nuclease in piRNA biogenesis. Nature 491:279–83
    [Google Scholar]
  59. 58.  Ishizu H, Iwasaki YW, Hirakata S, Ozaki H, Iwasaki W et al. 2015. Somatic primary piRNA biogenesis driven by cis-acting RNA elements and trans-acting Yb. Cell Rep 12:429–40
    [Google Scholar]
  60. 59.  Iwasaki YW, Murano K, Ishizu H, Shibuya A, Iyoda Y et al. 2016. Piwi modulates chromatin accessibility by regulating multiple factors including histone H1 to repress transposons. Mol. Cell 63:408–19
    [Google Scholar]
  61. 60.  Izumi N, Shoji K, Sakaguchi Y, Honda S, Kirino Y et al. 2016. Identification and functional analysis of the pre-piRNA 3′ Trimmer in silkworms. Cell 164:962–73
    [Google Scholar]
  62. 61.  Juliano CE, Reich A, Liu N, Götzfried J, Zhong M et al. 2014. PIWI proteins and PIWI-interacting RNAs function in Hydra somatic stem cells. PNAS 111:337–42
    [Google Scholar]
  63. 62.  Kaufmann J, Smale ST 1994. Direct recognition of initiator elements by a component of the transcription factor IID complex. Genes Dev 8:821–29
    [Google Scholar]
  64. 63.  Kawaoka S, Hara K, Shoji K, Kobayashi M, Shimada T et al. 2013. The comprehensive epigenome map of piRNA clusters. Nucleic Acids Res 41:1581–90
    [Google Scholar]
  65. 64.  Kawaoka S, Hayashi N, Suzuki Y, Abe H, Sugano S et al. 2009. The Bombyx ovary-derived cell line endogenously expresses PIWI/PIWI-interacting RNA complexes. RNA 15:1258–64
    [Google Scholar]
  66. 65.  Kawaoka S, Izumi N, Katsuma S, Tomari Y 2011. 3′ end formation of PIWI-interacting RNAs in vitro. Mol. Cell 43:1015–22
    [Google Scholar]
  67. 66.  Kelleher ES, Edelman NB, Barbash DA 2012. Drosophila interspecific hybrids phenocopy piRNA-pathway mutants. PLOS Biol 10:e1001428
    [Google Scholar]
  68. 67.  Khurana JS, Wang J, Xu J, Koppetsch BS, Thomson TC et al. 2011. Adaptation to P element transposon invasion in Drosophila melanogaster. Cell 147:1551–63
    [Google Scholar]
  69. 68.  Kidwell MG, Kidwell JF, Sved JA 1977. Hybrid dysgenesis in Drosophila melanogaster: a syndrome of aberrant traits including mutation, sterility and male recombination. Genetics 86:813–33
    [Google Scholar]
  70. 69.  Kirino Y, Kim N, de Planell-Saguer M, Khandros E, Chiorean S et al. 2009. Arginine methylation of Piwi proteins catalysed by dPRMT5 is required for Ago3 and Aub stability. Nat. Cell Biol. 11:652–58
    [Google Scholar]
  71. 70.  Kiuchi T, Koga H, Kawamoto M, Shoji K, Sakai H et al. 2014. A single female-specific piRNA is the primary determiner of sex in the silkworm. Nature 509:633–36
    [Google Scholar]
  72. 71.  Klattenhoff C, Xi H, Li C, Lee S, Xu J et al. 2009. The Drosophila HP1 homolog Rhino is required for transposon silencing and piRNA production by dual-strand clusters. Cell 138:1137–49
    [Google Scholar]
  73. 72.  Klenov MS, Lavrov SA, Korbut AP, Stolyarenko AD, Yakushev EY et al. 2014. Impact of nuclear Piwi elimination on chromatin state in Drosophila melanogaster ovaries. Nucleic Acids Res 42:6208–18
    [Google Scholar]
  74. 73.  Klenov MS, Sokolova OA, Yakushev EY, Stolyarenko AD, Mikhaleva EA et al. 2011. Separation of stem cell maintenance and transposon silencing functions of Piwi protein. PNAS 108:18760–65
    [Google Scholar]
  75. 74.  Kowalik KM, Shimada Y, Flury V, Stadler MB, Batki J, Bühler M 2015. The Paf1 complex represses small-RNA-mediated epigenetic gene silencing. Nature 520:248–52
    [Google Scholar]
  76. 75.  Larson AG, Elnatan D, Keenen MM, Trnka MJ, Johnston JB et al. 2017. Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin. Nature 547:236–40
    [Google Scholar]
  77. 76.  Lau NC, Robine N, Martin R, Chung W-J, Niki Y et al. 2009. Abundant primary piRNAs, endo-siRNAs, and microRNAs in a Drosophila ovary cell line. Genome Res 19:1776–85
    [Google Scholar]
  78. 77.  Lau NC, Seto AG, Kim J, Kuramochi-Miyagawa S, Nakano T et al. 2006. Characterization of the piRNA complex from rat testes. Science 313:363–67
    [Google Scholar]
  79. 78.  Le Thomas A, Rogers AK, Webster A, Marinov GK, Liao SE et al. 2013. Piwi induces piRNA-guided transcriptional silencing and establishment of a repressive chromatin state. Genes Dev 27:390–99
    [Google Scholar]
  80. 79.  Le Thomas A, Stuwe E, Li S, Du J, Marinov G et al. 2014. Transgenerationally inherited piRNAs trigger piRNA biogenesis by changing the chromatin of piRNA clusters and inducing precursor processing. Genes Dev 28:1667–80
    [Google Scholar]
  81. 80.  Lee H-C, Gu W, Shirayama M, Youngman E, Conte D Jr., Mello CC 2012. C. elegans piRNAs mediate the genome-wide surveillance of germline transcripts. Cell 150:78–87
    [Google Scholar]
  82. 81.  Lewis SH, Quarles KA, Yang Y, Tanguy M, Frézal L et al. 2018. Pan-arthropod analysis reveals somatic piRNAs as an ancestral defence against transposable elements. Nat. Ecol. Evol. 2:174–81
    [Google Scholar]
  83. 82.  Li C, Vagin VV, Lee S, Xu J, Ma S et al. 2009. Collapse of germline piRNAs in the absence of Argonaute3 reveals somatic piRNAs in flies. Cell 137:509–21
    [Google Scholar]
  84. 83.  Li XZ, Roy CK, Dong X, Bolcun-Filas E, Wang J et al. 2013. An ancient transcription factor initiates the burst of piRNA production during early meiosis in mouse testes. Mol. Cell 50:67–81
    [Google Scholar]
  85. 84.  Lim AK, Kai T 2007. Unique germ-line organelle, nuage, functions to repress selfish genetic elements in Drosophila melanogaster. PNAS 104:6714–19
    [Google Scholar]
  86. 85.  Lim RSM, Anand A, Nishimiya-Fujisawa C, Kobayashi S, Kai T 2014. Analysis of Hydra PIWI proteins and piRNAs uncover early evolutionary origins of the piRNA pathway. Dev. Biol. 386:237–51
    [Google Scholar]
  87. 86.  Liu L, Qi H, Wang J, Lin H 2011. PAPI, a novel TUDOR-domain protein, complexes with AGO3, ME31B and TRAL in the nuage to silence transposition. Development 138:1863–73
    [Google Scholar]
  88. 87.  Luteijn MJ, van Bergeijk P, Kaaij LJT, Almeida MV, Roovers EF et al. 2012. Extremely stable Piwi-induced gene silencing in Caenorhabditis elegans. EMBO J 31:3422–30
    [Google Scholar]
  89. 88.  Ma L, Buchold GM, Greenbaum MP, Roy A, Burns KH et al. 2009. GASZ is essential for male meiosis and suppression of retrotransposon expression in the male germline. PLOS Genet 5:e1000635
    [Google Scholar]
  90. 89.  Malone CD, Brennecke J, Dus M, Stark A, McCombie WR et al. 2009. Specialized piRNA pathways act in germline and somatic tissues of the Drosophila ovary. Cell 137:522–35
    [Google Scholar]
  91. 90.  Matsumoto N, Nishimasu H, Sakakibara K, Nishida KM, Hirano T et al. 2016. Crystal structure of silkworm PIWI-clade Argonaute Siwi bound to piRNA. Cell 167:484–97.e9
    [Google Scholar]
  92. 91.  Matsumoto N, Sato K, Nishimasu H, Namba Y, Miyakubi K et al. 2015. Crystal structure and activity of the endoribonuclease domain of the piRNA pathway factor Maelstrom. Cell Rep 11:366–75
    [Google Scholar]
  93. 92.  Megosh HB, Cox DN, Campbell C, Lin H 2006. The role of PIWI and the miRNA machinery in Drosophila germline determination. Curr. Biol. 16:1884–94
    [Google Scholar]
  94. 93.  Mendez DL, Mandt RE, Elgin SC 2013. Heterochromatin protein 1a (HP1a) partner specificity is determined by critical amino acids in the chromo shadow domain and C-terminal extension. J. Biol. Chem. 288:22315–23
    [Google Scholar]
  95. 94.  Miesen P, Girardi E, van Rij RP 2015. Distinct sets of PIWI proteins produce arbovirus and transposon-derived piRNAs in Aedes aegypti mosquito cells. Nucleic Acids Res 43:6545–56
    [Google Scholar]
  96. 95.  Mohn F, Handler D, Brennecke J 2015. piRNA-guided slicing specifies transcripts for Zucchini-dependent, phased piRNA biogenesis. Science 348:812–17
    [Google Scholar]
  97. 96.  Mohn F, Sienski G, Handler D, Brennecke J 2014. The Rhino-Deadlock-Cutoff complex licenses noncanonical transcription of dual-strand piRNA clusters in Drosophila. Cell 157:1364–79
    [Google Scholar]
  98. 97.  Morazzani EM, Wiley MR, Murreddu MG, Adelman ZN, Myles KM 2012. Production of virus-derived ping-pong-dependent piRNA-like small RNAs in the mosquito soma. PLOS Pathog 8:e1002470
    [Google Scholar]
  99. 98.  Motamedi MR, Verdel A, Colmenares SU, Gerber SA, Gygi SP, Moazed D 2004. Two RNAi complexes, RITS and RDRC, physically interact and localize to noncoding centromeric RNAs. Cell 119:789–802
    [Google Scholar]
  100. 99.  Muerdter F, Guzzardo PM, Gillis J, Luo Y, Yu Y et al. 2013. A genome-wide RNAi screen draws a genetic framework for transposon control and primary piRNA biogenesis in Drosophila. Mol. Cell 50:736–48
    [Google Scholar]
  101. 100.  Murota Y, Ishizu H, Nakagawa S, Iwasaki YW, Shibata S et al. 2014. Yb integrates piRNA intermediates and processing factors into perinuclear bodies to enhance piRISC assembly. Cell Rep 8:103–13
    [Google Scholar]
  102. 101.  Nishida KM, Iwasaki YW, Murota Y, Nagao A, Mannen T et al. 2015. Respective functions of two distinct Siwi complexes assembled during PIWI-interacting RNA biogenesis in Bombyx germ cells. Cell Rep 10:193–203
    [Google Scholar]
  103. 102.  Nishida KM, Okada TN, Kawamura T, Mituyama T, Kawamura Y et al. 2009. Functional involvement of Tudor and dPRMT5 in the piRNA processing pathway in Drosophila germlines. EMBO J 28:3820–31
    [Google Scholar]
  104. 103.  Nishimasu H, Ishizu H, Saito K, Fukuhara S, Kamatani MK et al. 2012. Structure and function of Zucchini endoribonuclease in piRNA biogenesis. Nature 491:284–87
    [Google Scholar]
  105. 104.  Ohtani H, Iwasaki YW, Shibuya A, Siomi H, Siomi MC, Saito K 2013. DmGTSF1 is necessary for Piwi–piRISC-mediated transcriptional transposon silencing in the Drosophila ovary. Genes Dev 27:1656–61
    [Google Scholar]
  106. 105.  Olivieri D, Senti K-A, Subramanian S, Sachidanandam R, Brennecke J 2012. The cochaperone shutdown defines a group of biogenesis factors essential for all piRNA populations in Drosophila. Mol. Cell 47:954–69
    [Google Scholar]
  107. 106.  Olivieri D, Sykora MM, Sachidanandam R, Mechtler K, Brennecke J 2010. An in vivo RNAi assay identifies major genetic and cellular requirements for primary piRNA biogenesis in Drosophila. EMBO J 29:3301–17
    [Google Scholar]
  108. 107.  Pandey RR, Homolka D, Chen K-M, Sachidanandam R, Fauvarque M-O, Pillai RS 2017. Recruitment of Armitage and Yb to a transcript triggers its phased processing into primary piRNAs in Drosophila ovaries. PLOS Genet 13:e1006956
    [Google Scholar]
  109. 108.  Pane A, Jiang P, Zhao DY, Singh M, Schüpbach T 2011. The Cutoff protein regulates piRNA cluster expression and piRNA production in the Drosophila germline. EMBO J 30:4601–15
    [Google Scholar]
  110. 109.  Pane A, Wehr K, Schüpbach T 2007. zucchini and squash encode two putative nucleases required for rasiRNA production in the Drosophila germline. Dev. Cell 12:851–62
    [Google Scholar]
  111. 110.  Parhad SS, Tu S, Weng Z, Theurkauf WE 2017. Adaptive evolution leads to cross-species incompatibility in the piRNA transposon silencing machinery. Dev. Cell 43:60–70.e5
    [Google Scholar]
  112. 111.  Patil VS, Anand A, Chakrabarti A, Kai T 2014. The Tudor domain protein Tapas, a homolog of the vertebrate Tdrd7, functions in the piRNA pathway to regulate retrotransposons in germline of Drosophila melanogaster. BMC Biol 12:61
    [Google Scholar]
  113. 112.  Patil VS, Kai T 2010. Repression of retroelements in Drosophila germline via piRNA pathway by the Tudor domain protein Tejas. Curr. Biol. 20:724–30
    [Google Scholar]
  114. 113.  Pélisson A, Song SU, Prud'homme N, Smith PA, Bucheton A, Corces VG 1994. Gypsy transposition correlates with the production of a retroviral envelope-like protein under the tissue-specific control of the Drosophila flamenco gene. EMBO J 13:4401–11
    [Google Scholar]
  115. 114.  Pezic D, Manakov SA, Sachidanandam R, Aravin AA 2014. piRNA pathway targets active LINE1 elements to establish the repressive H3K9me3 mark in germ cells. Genes Dev 28:1410–28
    [Google Scholar]
  116. 115.  Post C, Clark JP, Sytnikova YA, Chirn G-W, Lau NC 2014. The capacity of target silencing by Drosophila PIWI and piRNAs. RNA 20:1977–86
    [Google Scholar]
  117. 116.  Preall JB, Czech B, Guzzardo PM, Muerdter F, Hannon GJ 2012. shutdown is a component of the Drosophila piRNA biogenesis machinery. RNA 18:1446–57
    [Google Scholar]
  118. 117.  Prud'homme N, Gans M, Masson M, Terzian C, Bucheton A 1995. Flamenco, a gene controlling the gypsy retrovirus of Drosophila melanogaster. Genetics 139:697–711
    [Google Scholar]
  119. 118.  Purnell BA, Emanuel PA, Gilmour DS 1994. TFIID sequence recognition of the initiator and sequences farther downstream in Drosophila class II genes. Genes Dev 8:830–42
    [Google Scholar]
  120. 119.  Qi H, Watanabe T, Ku H-Y, Liu N, Zhong M, Lin H 2011. 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. 286:3789–97
    [Google Scholar]
  121. 120.  Rangan P, Malone CD, Navarro C, Newbold SP, Hayes PS et al. 2011. piRNA production requires heterochromatin formation in Drosophila. Curr. Biol. 21:1373–79
    [Google Scholar]
  122. 121.  Reuter M, Berninger P, Chuma S, Shah H, Hosokawa M et al. 2011. Miwi catalysis is required for piRNA amplification-independent LINE1 transposon silencing. Nature 480:264–67
    [Google Scholar]
  123. 122.  Reuter M, Chuma S, Tanaka T, Franz T, Stark A, Pillai RS 2009. Loss of the Mili-interacting Tudor domain-containing protein-1 activates transposons and alters the Mili-associated small RNA profile. Nat. Struct. Mol. Biol. 16:639–46
    [Google Scholar]
  124. 123.  Robine N, Lau NC, Balla S, Jin Z, Okamura K et al. 2009. A broadly conserved pathway generates 3′UTR-directed primary piRNAs. Curr. Biol. 19:2066–76
    [Google Scholar]
  125. 124.  Rogers AK, Situ K, Perkins EM, Toth KF 2017. Zucchini-dependent piRNA processing is triggered by recruitment to the cytoplasmic processing machinery. Genes Dev 31:1858–69
    [Google Scholar]
  126. 125.  Rozhkov NV, Hammell M, Hannon GJ 2013. Multiple roles for Piwi in silencing Drosophila transposons. Genes Dev 27:400–12
    [Google Scholar]
  127. 126.  Ruby JG, Jan C, Player C, Axtell MJ, Lee W et al. 2006. Large-scale sequencing reveals 21U-RNAs and additional microRNAs and endogenous siRNAs in C. elegans. Cell 127:1193–207
    [Google Scholar]
  128. 127.  Rudolph T, Yonezawa M, Lein S, Heidrich K, Kubicek S et al. 2007. Heterochromatin formation in Drosophila is initiated through active removal of H3K4 methylation by the LSD1 homolog SU(VAR)3-3. Mol. Cell 26:103–15
    [Google Scholar]
  129. 128.  Saito K, Inagaki S, Mituyama T, Kawamura Y, Ono Y et al. 2009. A regulatory circuit for piwi by the large Maf gene traffic jam in Drosophila. Nature 461:1296–99
    [Google Scholar]
  130. 129.  Saito K, Ishizu H, Komai M, Kotani H, Kawamura Y et al. 2010. Roles for the Yb body components Armitage and Yb in primary piRNA biogenesis in Drosophila. Genes Dev 24:2493–98
    [Google Scholar]
  131. 130.  Saito K, Nishida KM, Mori T, Kawamura Y, Miyoshi K et al. 2006. Specific association of Piwi with rasiRNAs derived from retrotransposon and heterochromatic regions in the Drosophila genome. Genes Dev 20:2214–22
    [Google Scholar]
  132. 131.  Saito K, Sakaguchi Y, Suzuki T, Suzuki T, Siomi H, Siomi MC 2007. Pimet, the Drosophila homolog of HEN1, mediates 2′-O-methylation of Piwi-interacting RNAs at their 3′ ends. Genes Dev 21:1603–8
    [Google Scholar]
  133. 132.  Sato K, Iwasaki YW, Shibuya A, Carninci P, Tsuchizawa Y et al. 2015. Krimper enforces an antisense bias on piRNA pools by binding AGO3 in the Drosophila germline. Mol. Cell 59:553–63
    [Google Scholar]
  134. 133.  Saxe JP, Chen M, Zhao H, Lin H 2013. Tdrkh is essential for spermatogenesis and participates in primary piRNA biogenesis in the germline. EMBO J 32:1869–85
    [Google Scholar]
  135. 134.  Senti K-A, Jurczak D, Sachidanandam R, Brennecke J 2015. piRNA-guided slicing of transposon transcripts enforces their transcriptional silencing via specifying the nuclear piRNA repertoire. Genes Dev 29:1747–62
    [Google Scholar]
  136. 135.  Sheu-Gruttadauria J, MacRae IJ 2017. Structural foundations of RNA silencing by Argonaute. J. Mol. Biol. 429:2619–39
    [Google Scholar]
  137. 136.  Shimada Y, Mohn F, Bühler M 2016. The RNA-induced transcriptional silencing complex targets chromatin exclusively via interacting with nascent transcripts. Genes Dev 30:2571–80
    [Google Scholar]
  138. 137.  Shirayama M, Seth M, Lee H-C, Gu W, Ishidate T et al. 2012. piRNAs initiate an epigenetic memory of nonself RNA in the C. elegans germline. Cell 150:65–77
    [Google Scholar]
  139. 138.  Shiromoto Y, Kuramochi-Miyagawa S, Daiba A, Chuma S, Katanaya A et al. 2013. GPAT2, a mitochondrial outer membrane protein, in piRNA biogenesis in germline stem cells. RNA 19:803–10
    [Google Scholar]
  140. 139.  Shoji M, Tanaka T, Hosokawa M, Reuter M, Stark A et al. 2009. The TDRD9-MIWI2 complex is essential for piRNA-mediated retrotransposon silencing in the mouse male germline. Dev. Cell 17:775–87
    [Google Scholar]
  141. 140.  Sienski G, Batki J, Senti K-A, Dönertas D, Tirian L et al. 2015. Silencio/CG9754 connects the Piwi–piRNA complex to the cellular heterochromatin machinery. Genes Dev 29:2258–71
    [Google Scholar]
  142. 141.  Sienski G, Dönertas D, Brennecke J 2012. Transcriptional silencing of transposons by Piwi and maelstrom and its impact on chromatin state and gene expression. Cell 151:964–80
    [Google Scholar]
  143. 142.  Strom AR, Emelyanov AV, Mir M, Fyodorov DV, Darzacq X, Karpen GH 2017. Phase separation drives heterochromatin domain formation. Nature 547:241–45
    [Google Scholar]
  144. 143.  Sugiyama T, Cam H, Verdel A, Moazed D, Grewal SI 2005. RNA-dependent RNA polymerase is an essential component of a self-enforcing loop coupling heterochromatin assembly to siRNA production. PNAS 102:152–57
    [Google Scholar]
  145. 144.  Sumiyoshi T, Sato K, Yamamoto H, Iwasaki YW, Siomi H, Siomi MC 2016. Loss of l(3)mbt leads to acquisition of the ping-pong cycle in Drosophila ovarian somatic cells. Genes Dev 30:1617–22
    [Google Scholar]
  146. 145.  Szakmary A, Reedy M, Qi H, Lin H 2009. The Yb protein defines a novel organelle and regulates male germline stem cell self-renewal in Drosophila melanogaster. J. Cell Biol 185:613–27
    [Google Scholar]
  147. 146.  Tang W, Tu S, Lee H-C, Weng Z, Mello CC 2016. The RNase PARN-1 trims piRNA 3′ ends to promote transcriptome surveillance in C. elegans. Cell 164:974–84
    [Google Scholar]
  148. 147.  Teixeira FK, Okuniewska M, Malone CD, Coux R-X, Rio DC, Lehmann R 2017. piRNA-mediated regulation of transposon alternative splicing in the soma and germ line. Nature 552:268–72
    [Google Scholar]
  149. 148.  Tyc KM, Nabih A, Wu MZ, Wedeles CJ, Sobotka JA, Claycomb JM 2017. The conserved intron binding protein EMB-4 plays differential roles in germline small RNA pathways of C. elegans. Dev. Cell 42:256–70.e6
    [Google Scholar]
  150. 149.  Vagin VV, Sigova A, Li C, Seitz H, Gvozdev V, Zamore PD 2006. A distinct small RNA pathway silences selfish genetic elements in the germline. Science 313:320–24
    [Google Scholar]
  151. 150.  Vagin VV, Wohlschlegel J, Qu J, Jonsson Z, Huang X et al. 2009. Proteomic analysis of murine Piwi proteins reveals a role for arginine methylation in specifying interaction with Tudor family members. Genes Dev 23:1749–62
    [Google Scholar]
  152. 151.  Vagin VV, Yu Y, Jankowska A, Luo Y, Wasik KA et al. 2013. Minotaur is critical for primary piRNA biogenesis. RNA 19:1064–77
    [Google Scholar]
  153. 152.  Verdel A, Jia S, Gerber S, Sugiyama T, Gygi S et al. 2004. RNAi-mediated targeting of heterochromatin by the RITS complex. Science 303:672–76
    [Google Scholar]
  154. 153.  Voigt F, Reuter M, Kasaruho A, Schulz EC, Pillai RS, Barabas O 2012. Crystal structure of the primary piRNA biogenesis factor Zucchini reveals similarity to the bacterial PLD endonuclease Nuc. RNA 18:2128–34
    [Google Scholar]
  155. 154.  Vourekas A, Zheng K, Fu Q, Maragkakis M, Alexiou P et al. 2015. The RNA helicase MOV10L1 binds piRNA precursors to initiate piRNA processing. Genes Dev 29:617–29
    [Google Scholar]
  156. 155.  Wang SH, Elgin SCR 2011. Drosophila Piwi functions downstream of piRNA production mediating a chromatin-based transposon silencing mechanism in female germ line. PNAS 108:21164–69
    [Google Scholar]
  157. 156.  Wang W, Han BW, Tipping C, Ge DT, Zhang Z et al. 2015. Slicing and binding by Ago3 or Aub trigger Piwi-bound piRNA production by distinct mechanisms. Mol. Cell 59:819–30
    [Google Scholar]
  158. 157.  Watanabe T, Chuma S, Yamamoto Y, Kuramochi-Miyagawa S, Totoki Y et al. 2011. MITOPLD is a mitochondrial protein essential for nuage formation and piRNA biogenesis in the mouse germline. Dev. Cell 20:364–75
    [Google Scholar]
  159. 158.  Webster A, Li S, Hur JK, Wachsmuth M, Bois JS et al. 2015. Aub and Ago3 are recruited to Nuage through two mechanisms to form a ping-pong complex assembled by Krimper. Mol. Cell 59:564–75
    [Google Scholar]
  160. 159.  Weick E-M, Sarkies P, Silva N, Chen RA, Moss SMM et al. 2014. PRDE-1 is a nuclear factor essential for the biogenesis of Ruby motif-dependent piRNAs in C. elegans. Genes Dev 28:783–96
    [Google Scholar]
  161. 160.  Wenda JM, Homolka D, Yang Z, Spinelli P, Sachidanandam R et al. 2017. Distinct roles of RNA helicases MVH and TDRD9 in PIWI slicing-triggered mammalian piRNA biogenesis and function. Dev. Cell 41:623–37.e9
    [Google Scholar]
  162. 161.  Xiang S, Cooper-Morgan A, Jiao X, Kiledjian M, Manley JL, Tong L 2009. Structure and function of the 5′→3′ exoribonuclease Rat1 and its activating partner Rai1. Nature 458:784–88
    [Google Scholar]
  163. 162.  Xiol J, Cora E, Koglgruber R, Chuma S, Subramanian S et al. 2012. A role for Fkbp6 and the chaperone machinery in piRNA amplification and transposon silencing. Mol. Cell 47:970–79
    [Google Scholar]
  164. 163.  Yang Z, Chen K-M, Pandey RR, Homolka D, Reuter M et al. 2016. PIWI slicing and EXD1 drive biogenesis of nuclear piRNAs from cytosolic targets of the mouse piRNA pathway. Mol. Cell 61:138–52
    [Google Scholar]
  165. 163a.  Yashiro R, Murota Y, Nishida KM, Yamashiro H, Fujii K et al. 2018. Piwi nuclear localization and its regulatory mechanism in Drosophila ovarian somatic cells. Cell Rep. 23:3647–57
    [Google Scholar]
  166. 164.  Yin H, Lin H 2007. An epigenetic activation role of Piwi and a Piwi-associated piRNA in Drosophila melanogaster. Nature 450:304–8
    [Google Scholar]
  167. 164a.  Yu B, Lin YA, Parhad SS, Jin Z, Ma J et al. 2018. Structural insights into Rhino–Deadlock complex for germline piRNA cluster specification. EMBO Rep. 19:e45418
    [Google Scholar]
  168. 165.  Yu Y, Gu J, Jin Y, Luo Y, Preall JB et al. 2015. Panoramix enforces piRNA-dependent cotranscriptional silencing. Science 350:339–42
    [Google Scholar]
  169. 166.  Yuan K, O'Farrell PH 2016. TALE-light imaging reveals maternally guided, H3K9me2/3-independent emergence of functional heterochromatin in Drosophila embryos. Genes Dev 30:579–93
    [Google Scholar]
  170. 167.  Zamparini AL, Davis MY, Malone CD, Vieira E, Zavadil J et al. 2011. Vreteno, a gonad-specific protein, is essential for germline development and primary piRNA biogenesis in Drosophila. Development 138:4039–50
    [Google Scholar]
  171. 168.  Zenk F, Loeser E, Schiavo R, Kilpert F, Bogdanović O, Iovino N 2017. Germ line-inherited H3K27me3 restricts enhancer function during maternal-to-zygotic transition. Science 357:212–16
    [Google Scholar]
  172. 169.  Zhang F, Wang J, Xu J, Zhang Z, Koppetsch BS et al. 2012. UAP56 couples piRNA clusters to the perinuclear transposon silencing machinery. Cell 151:871–84
    [Google Scholar]
  173. 170.  Zhang K, Mosch K, Fischle W, Grewal SIS 2008. Roles of the Clr4 methyltransferase complex in nucleation, spreading and maintenance of heterochromatin. Nat. Struct. Mol. Biol. 15:381–88
    [Google Scholar]
  174. 171.  Zhang Z, Wang J, Schultz N, Zhang F, Parhad SS et al. 2014. The HP1 homolog Rhino anchors a nuclear complex that suppresses piRNA precursor splicing. Cell 157:1353–63
    [Google Scholar]
  175. 172.  Zhang Z, Xu J, Koppetsch BS, Wang J, Tipping C et al. 2011. Heterotypic piRNA Ping-Pong requires Qin, a protein with both E3 ligase and Tudor domains. Mol. Cell 44:572–84
    [Google Scholar]
  176. 173.  Zheng K, Xiol J, Reuter M, Eckardt S, Leu NA et al. 2010. Mouse MOV10L1 associates with Piwi proteins and is an essential component of the Piwi-interacting RNA (piRNA) pathway. PNAS 107:11841–46
    [Google Scholar]
  177. 174.  Zhong X, Du J, Hale CJ, Gallego-Bartolome J, Feng S et al. 2014. Molecular mechanism of action of plant DRM de novo DNA methyltransferases. Cell 157:1050–60
    [Google Scholar]
  178. 175.  Zhou X, Battistoni G, El Demerdash O, Gurtowski J, Wunderer J et al. 2015. Dual functions of Macpiwi1 in transposon silencing and stem cell maintenance in the flatworm Macrostomum lignano. RNA 21:1885–97
    [Google Scholar]
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