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piRNAs-Transposon Silencing and Germ Line Development

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Genomic Elements in Health, Disease and Evolution

Abstract

Transposable elements (TEs), can insert themselves independently into genomes and alter the genome structure and consequently the function of genes. The repression of TE expression and transposition is of primary importance especially to germ line cells since they are the only cells that will pass the genetic information onto the next generation. In animals, including mammals, the evolutionary conserved subclass of the Argonaute proteins, the P-element induced wimpy testis proteins (PIWI), play a central role in the silencing of TEs during gametogenesis. PIWI proteins bind a class of small non-coding RNAs, called piRNAs (24–32 nucleotides long), to form the piRNA-inducing silencing complex (piRISC). piRISC represses TE transcription via epigenetic modifications, and TE mobilization via PIWI-catalyzed degradation of TE-RNA. PIWI proteins are also involved in the biogenesis of piRNAs from precursor RNA molecules that originate in conserved DNA regions (clusters) containing non-coding sequences or TE repeat sequences. The piRISC-mediated TE repression and piRNA biogenesis are modulated through associations with cytoplasmic proteins that act as scaffolds for piRISC localization, mobilization and activity. The precise mechanism and the full repertoire of proteins involved in the piRNA-PIWI pathway are currently under investigation. Experimental animal models from diverse phyla and species indicate that this pathway has been conserved in metazoan, through evolution. It has evolved through Piwi gene duplications and piRNA cluster expansions to defend in a cell and tissue-specific context, the integrity of the genome during germ line development. Recent evidence indicates that the biological functions of the piRNA-PIWI system may extend beyond transposon control and be involved in the regulation of the expression of protein-coding genes that determine male germ cell specification, self-renewal and maturation. Dysfunctions of the piRNA-PIWI pathway causing TE accumulation may result in fertility defects; similarly irregularities in PIWI function may underlie causes for cancer development in mammals.

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References

  1. Biémont C (2010) A brief history of the status of transposable elements: from junk DNA to major players. Evolution 186:1085–1093

    Google Scholar 

  2. Zamudio N, Bourc'his D (2010) Transposable elements in the mammalian germ line: a comfortable niche or a deadly trap? Heredity 105:92–104

    Article  CAS  PubMed  Google Scholar 

  3. Hua-Van A, Le Rouzic A, Boutin TS, Filee J, Capy P (2011) The struggle for life of the genome’s selfish architects. Biol Direct 6:19

    Article  PubMed Central  PubMed  Google Scholar 

  4. Murr R (2010) Interplay between different epigenetic modifications and mechanisms. Adv Genet 70:101–141

    Article  CAS  PubMed  Google Scholar 

  5. Ballestar E (2011) An introduction to epigenetics. Adv Exp Med Biol 711:1–11

    Article  CAS  PubMed  Google Scholar 

  6. Jones PA (2012) Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet 13:484–492

    Article  CAS  PubMed  Google Scholar 

  7. Cui I, Cui H (2010) Antisense RNAs and epigenetic regulation. Epigenomics 2:139–150

    Article  CAS  PubMed  Google Scholar 

  8. Malecová B, Morris KV (2010) Transcriptional gene silencing mediated by non-coding RNAs. Curr Opin Mol Ther 12:214–222

    PubMed Central  PubMed  Google Scholar 

  9. Zhou H, Hu H, Lai M (2010) Non-coding RNAs and their epigenetic regulatory mechanisms. Biol Cell 102:645–655

    Article  CAS  PubMed  Google Scholar 

  10. Zamore PD, Tuschl T, Sharp PA, Bartel DP (2000) RNAi: double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell 101(1):25–33

    Article  CAS  PubMed  Google Scholar 

  11. Kooter JM, Matzke MA, Meyer P (1999) Listening to the silent genes: transgene silencing, gene regulation and pathogen control. Trends Plant Sci 4:340–347

    Article  PubMed  Google Scholar 

  12. Hartig JV, Tomari Y, Förstemann K (2007) piRNAs-the ancient hunters of genome invaders. Genes Dev 21:1707–1713

    Article  CAS  PubMed  Google Scholar 

  13. Su C, Ren ZJ, Wang F, Liu M, Li X, Tang H (2012) PIWIL4 regulates cervical cancer cell line growth and is involved in down-regulating the expression of p14ARF and p53. FEBS Lett 586:1356–1362

    Article  CAS  PubMed  Google Scholar 

  14. Wang G, Reinke V (2008) A C. Elegans Piwi, PRG−1, regulates 21U-RNAs during spermatogenesis. Curr Biol 18:861–867

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Kim VN, Han J, Siomi MC (2009) Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol 10:126–139

    Article  CAS  PubMed  Google Scholar 

  16. Ghildiyal M, Zamore PD (2009) Small silencing RNAs: an expanding universe. Nat Rev Genet 10:94–108

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Malone CD, Hannon GJ (2009) Small RNAs as guardians of the genome. Cell 136(4):656–668

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Girard A, Hannon GJ (2008) Conserved themes in small-RNA-mediated transposon control. Trends Cell Biol 18:136–148

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Lau NC, Robine N, Martin R, Chung WJ, Niki Y, Berezikov E, Lai EC (2009) Abundant primary piRNAs, endo-siRNAs, and microRNAs in a Drosophila ovary cell line. Genome Res 19:1776–1785

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Siomi MC, Sato K, Pezic D, Aravin AA (2011) PIWI-interacting small RNAs: the vanguard of genome defence. Nat Rev Mol Cell Biol 12:246–258

    Article  CAS  PubMed  Google Scholar 

  21. Rozhkov NV, Hammell M, Hannon GJ (2013) Multiple roles for Piwi in silencing Drosophila transposons. Genes Dev 27:400–412

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Juliano C, Wang J, Lin H (2011) Uniting germline and stem cells: the function of Piwi proteins and the piRNA pathway in diverse organisms. Annu Rev Genet 45:447–469

    Article  CAS  PubMed  Google Scholar 

  23. Pillai RS, Chuma S (2012) piRNAs and their involvement in male germline development in mice. Dev Growth Differ 54(1):78–92

    Article  CAS  PubMed  Google Scholar 

  24. Simonelig M (2011) Developmental functions of piRNAs and transposable elements: a Drosophila point-of-view. RNA Biol 8:754–759

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Khurana JS, Theurkauf W (2010) piRNAs, transposon silencing, and Drosophila germline development. J Cell Biol 191:905–913

    Article  PubMed Central  PubMed  Google Scholar 

  26. Kota SK, Feil R (2010) Epigenetic transitions in germ cell development and meiosis. Dev Cell 19:675–686

    Article  CAS  PubMed  Google Scholar 

  27. De Felici M (2011) Nuclear reprogramming in mouse primordial germ cells: epigenetic contribution. Stem Cells Int 2011:e425863

    Article  CAS  Google Scholar 

  28. Lee TL, Pang AL, Rennert OM, Chan WY (2009) Genomic landscape of developing male germ cells. Birth Defects Res C Embryo Today 87:43–63

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Smallwood SA, Kelsey G (2012) De novo DNA methylation: a germ cell perspective. Trends Genet 28:33–42

    Article  CAS  PubMed  Google Scholar 

  30. Law JA, Jacobsen SE (2010) Establishing, maintaining and modifying DNA methylation patterns in plants and animals. Nat Rev Genet 11:204–220

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Grivna ST, Beyret E, Wang Z, Lin H (2006) A novel class of small RNAs in mouse spermatogenic cells. Genes Dev 20:1709–1714

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Aravin AA, Hannon GJ, Brennecke J (2007) The Piwi-piRNA pathway provides an adaptive defense in the transposon arms race. Science 318:761–764

    Article  CAS  PubMed  Google Scholar 

  33. Brennecke J, Aravin AA, Stark A, Dus M, Kellis M, Sachidanandam R, Hannon GJ (2007) Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila. Cell 128:1089–1103

    Article  CAS  PubMed  Google Scholar 

  34. Aravin AA, Hannon GJ (2008) Small RNA silencing pathways in germ and stem cells. Cold Spring Harb Symp Quant Biol 73:283–290

    Article  CAS  PubMed  Google Scholar 

  35. 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 313:320–324

    Article  CAS  PubMed  Google Scholar 

  36. Saito K, Nishida KM, Mori T, Kawamura Y, Miyoshi K, Nagami T, Siomi H, Siomi MC (2006) Specific association of Piwi with rasiRNAs derived from retrotransposon and heterochromatic regions in the Drosophila genome. Genes Dev 20:2214–2222

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Klattenhoff C, Theurkauf W (2008) Biogenesis and germ line functions of piRNAs. Development 135:3–9

    Article  CAS  PubMed  Google Scholar 

  38. Wang J, Saxe JP, Tanaka T, Chuma S, Lin H (2009) Mili interacts with Tudor domain-containing protein 1 in regulating spermatogenesis. Curr Biol 19:640–644

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Aravin AA, van der Heijden GW, Castaneda J, Vagin VV, Hannon GJ, Bortvin A (2009) Cytoplasmic compartmentalization of the fetal piRNA pathway in mice. PLoS Genet 5:e1000764

    Article  PubMed Central  PubMed  CAS  Google Scholar 

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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Kuramochi-Miyagawa S, Kimura T, Yomogida K, Kuroiwa A, Tadokoro Y, Fujita Y, Sato M, Matsuda Y, Nakano T (2001) Two mouse piwi-related genes: miwi and mili. Mech Dev 108:121–133

    Article  CAS  PubMed  Google Scholar 

  42. Deng W, Lin H (2002) miwi, a murine homolog of piwi, encodes a cytoplasmic protein essential for spermatogenesis. Dev Cell 2:819–830

    Article  CAS  PubMed  Google Scholar 

  43. Girard A, Sachidanandam R, Hannon GJ, Carmell MA (2006) A germ line-specific class of small RNAs binds mammalian Piwi proteins. Nature 442:199–202

    PubMed  Google Scholar 

  44. Lau NC, Seto AG, Kim J, Kuramochi-Miyagawa S, Nakano T, Bartel DP, Kingston RE (2006) Characterization of the piRNA complex from rat testes. Science 313:363–367

    Article  CAS  PubMed  Google Scholar 

  45. Carmell MA, Girard A, van de Kant HJ, Bourc'his D, Bestor TH, de Rooij DG, Hannon GJ (2007) MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline. Dev Cell 12:503–514

    Article  CAS  PubMed  Google Scholar 

  46. Houwing S, Kamminga LM, Berezikov E, Cronembold D, Girard A, van den Elst H, Filippov DV, Blaser H, Raz E, Moens CB, Plasterk RH, Hannon GJ, Draper BW, Ketting RF (2007) A role for Piwi and piRNAs in germ cell maintenance and transposon silencing in Zebrafish. Cell 129:69–82

    Article  CAS  PubMed  Google Scholar 

  47. Aravin A, Gaidatzis D, Pfeffer S, Lagos-Quintana M, Landgraf P, Iovino N, Morris P, Brownstein MJ, Kuramochi-Miyagawa S, Nakano T, Chien M, Russo JJ, Ju J, Sheridan R, Sander C, Zavolan M, Tuschl T (2006) A novel class of small RNAs bind to MILI protein in mouse testes. Nature 442:203–207

    CAS  PubMed  Google Scholar 

  48. Aravin AA, Sachidanandam R, Girard A, Fejes-Toth K, Hannon GJ (2007) Developmentally regulated piRNA clusters implicate MILI in transposon control. Science 316:744–747

    Article  CAS  PubMed  Google Scholar 

  49. Ku H-Y, Lin H (2014) PIWI proteins and their interactors in piRNA biogenesis, germline development and gene expression. Natl Sci Rev 1:205–218

    Article  PubMed Central  PubMed  Google Scholar 

  50. Malone CD, Brennecke J, Dus M, Stark A, McCombie WR, Sachidanandam R, Hannon GJ (2009) Specialized piRNA pathways act in germ line and somatic tissues of the drosophila ovary. Cell 137:522–535

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. Grimson A, Srivastava M, Fahey B, Woodcroft BJ, Chiang HR, King N, Degnan BM, Rokhsar DS, Bartel DP (2008) Early origins and evolution of microRNAs and Piwi-interacting RNAs in animals. Nature 455:1193–1197

    Article  CAS  PubMed  Google Scholar 

  52. Ohnishi Y, Totoki Y, Toyoda A, Watanabe T, Yamamoto Y, Tokunaga K, Sakaki Y, Sasaki H, Hohjoh H (2010) Small RNA class transition from siRNA/piRNA to miRNA during pre-implantation mouse development. Nucleic Acids Res 38(15):5141–5151

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  53. Gonzalez G, Behringer RR (2009) Dicer is required for female reproductive tract development and fertility in the mouse. Mol Reprod Dev 76:678–688

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  54. 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

    CAS  PubMed  Google Scholar 

  55. Thompson T, Lin H (2009) The biogenesis and function of PIWI proteins and piRNAs: progress and prospect. Annu Rev Cell Dev Biol 25:355–376

    Article  CAS  Google Scholar 

  56. Gagnon KT, Corey DR (2012) Argonaute and the nuclear RNAs: new pathways for RNA-mediated control of gene expression. Nucleic Acid Ther 22:3–16

    PubMed Central  CAS  PubMed  Google Scholar 

  57. Li C, Vagin VV, Lee S, Xu J, Ma S, Xi H, Seitz H, Horwich MD, Syrzycka M, Honda BM, Kittler EL, Zapp ML, Klattenhoff C, Schulz N, Theurkauf WE, Weng Z, Zamore PD (2009) Collapse of germ line piRNAs in the absence of Argonaute3 reveals somatic piRNAs in flies. Cell 137:509–521

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  58. Kuramochi-Miyagawa S, Watanabe T, Gotoh K, Totoki Y, Toyoda A, Ikawa M, Asada N, Kojima K, Yamaguchi Y, Ijiri TW, Hata K, Li E, Matsuda Y, Kimura T, Okabe M, Sakaki Y, Sasaki H, Nakano T (2008) DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes. Genes Dev 22:908–917

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  59. Unhavaithaya Y, Hao Y, Beyret E, Yin H, Kuramochi-Miyagawa S, Nakano T, Lin H (2009) MILI, a PIWI-interacting RNA-binding protein, is required for germ line stem cell self-renewal and appears to positively regulate translation. J Biol Chem 284:6507–6519

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  60. Le Thomas A, Rogers AK, Webster A, Marinov GK, Liao SE, Perkins EM, Hur JK, Aravin AA, Toth KF (2013) Piwi induces piRNA-guided transcriptional silencing and establishment of a repressive chromatin state. Genes Dev 27:390–399

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  61. Aravin AA, Bourc'his D (2008) Small RNA guides for de novo DNA methylation in mammalian germ cells. Genes Dev 22:970–975

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  62. Watanabe T, Tomizawa S, Mitsuya K, Totoki Y, Yamamoto Y, Kuramochi-Miyagawa S, Iida N, Hoki Y, Murphy PJ, Toyoda A, Gotoh K, Hiura H, Arima T, Fujiyama A, Sado T, Shibata T, Nakano T, Lin H, Ichiyanagi K, Soloway PD, Sasaki H (2011) Role for piRNAs and noncoding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus. Science 332:848–852

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  63. Reuter M, Berninger P, Chuma S, Shah H, Hosokawa M, Funaya C, Antony C, Sachidanandam R, Pillai RS (2011) Miwi catalysis is required for piRNA amplification-independent LINE1 transposon silencing. Nature 480:264–267

    Article  CAS  PubMed  Google Scholar 

  64. Beyret E, Lin H (2011) Pinpointing the expression of piRNAs and function of the PIWI protein subfamily during spermatogenesis in the mouse. Dev Biol 355:215–226

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  65. Vourekas A, Zheng Q, Alexiou P, Maragkakis M, Kirino Y, Gregory BD, Mourelatos Z (2012) Mili and Miwi target RNA repertoire reveals piRNA biogenesis and function of Miwi in spermiogenesis. Nat Struct Mol Biol 19:773–781

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  66. Gunawardane LS, Saito K, Nishida KM, Miyoshi K, Kawamura Y, Nagami T, Siomi H, Siomi MC (2007) A slicer-mediated mechanism for repeat-associated siRNA 5′ end formation in Drosophila. Science 315:1587–1590

    Article  CAS  PubMed  Google Scholar 

  67. Tam OH, Aravin AA, Stein P, Girard A, Murchison EP, Cheloufi S, Hodges E, Anger M, Sachidanandam R, Schultz RM, Hannon GJ (2008) Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes. Nature 453:534–538

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  68. Suh N, Blelloch R (2011) Small RNAs in early mammalian development: from gametes to gastrulation. Development 138(9):1653–1661

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  69. Lau NC (2010) Small RNAs in the animal gonad: guarding genomes and guiding development. Int J Biochem Cell Biol 42:1334–1347

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  70. Yin H, Lin H (2007) An epigenetic activation role of Piwi and a Piwi-associated piRNA in Drosophila melanogaster. Nature 450:304–308

    Article  CAS  PubMed  Google Scholar 

  71. Lu HL, Tanguy S, Rispe C, Gauthier JP, Walsh T, Gordon K, Edwards O, Tagu D, Chang CC, Jaubert-Possamai S (2011) Expansion of genes encoding piRNA-associated argonaute proteins in the pea aphid: diversification of expression profiles in different plastic morphs. PLoS One 6:e28051

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  72. Sasaki T, Shiohama A, Minoshima S, Shimizu N (2003) Identification of eight members of the Argonaute family in the human genome small star, filled. Genomics 82:323–330

    Article  CAS  PubMed  Google Scholar 

  73. Murphy D, Dancis B, Brown JR (2008) The evolution of core proteins involved in microRNA biogenesis. BMC Evol Biol 8:92

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  74. Qiao D, Zeeman AM, Deng W, Looijenga LH, Lin H (2002) Molecular characterization of hiwi, a human member of the piwi gene family whose over expression is correlated to seminomas. Oncogene 21:3988–3999

    Article  CAS  PubMed  Google Scholar 

  75. Sugimoto K, Kage H, Aki N, Sano A, Kitagawa H, Nagase T, Yatomi Y, Ohishi N, Takai D (2007) The induction of H3K9 methylation by PIWIL4 at the p16Ink4a locus. Biochem Biophys Res Commun 359:497–502

    Article  CAS  PubMed  Google Scholar 

  76. Jinek M, Doudna JA (2009) A three-dimensional view of the molecular machinery of RNA interference. Nature 457:405–412

    Article  CAS  PubMed  Google Scholar 

  77. Kirino Y, Mourelatos Z (2007) The mouse homolog of HEN1 is a potential methylase for Piwi-interacting RNAs. RNA 13:1397–1401

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  78. Parker JS, Parizotto EA, Wang M, Roe SM, Barford D (2009) Enhancement of the seed-target recognition step in RNA silencing by a PIWI/MID domain protein. Mol Cell 33:204–214

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  79. Tian Y, Simanshu DK, Ma JB, Patel DJ (2011) Structural basis for piRNA 2′-O-methylated 3′-end recognition by Piwi PAZ (Piwi/Argonaute/Zwille) domains. Proc Natl Acad Sci U S A 108:903–910

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  80. Nowotny M, Yang W (2009) Structural and functional modules in RNA interference. Curr Opin Struct Biol 19:286–293

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  81. Nguyen-Chi M, Morello D (2011) RNA-binding proteins, RNA granules, and gametes: is unity strength? Reproduction 142:803–817. doi:10.1530/REP-11-0257

    Article  CAS  PubMed  Google Scholar 

  82. Tan GS, Garchow BG, Liu X, Metzler D, Kiriakidou M (2011) Clarifying mammalian RISC assembly in vitro. BMC Mol Biol 12:19

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  83. De Fazio S, Bartonicek N, Di Giacomo M, Abreu-Goodger C, Sankar A, Funaya C, Antony C, Moreira PN, Enright AJ, O'Carroll D (2011) The endonuclease activity of Mili fuels piRNA amplification that silences LINE1 elements. Nature 480:259–263

    Article  PubMed  CAS  Google Scholar 

  84. Haase AD, Fenoglio S, Muerdter F, Guzzardo PM, Czech B, Pappin DJ, Chen C, Gordon A, Hannon GJ (2010) Probing the initiation and effector phases of the somatic piRNA pathway in Drosophila. Genes Dev 24(22):2499–2504

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  85. Sato K, Mishida KM, Shibuya A, Siomi MC, Siomi H (2011) Maelstrom coordinates microtubule organization during Drosophila oogenesis through interaction with components of the MTOC. Genes Dev 25:2361–2373

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  86. Siomi MC, Miyoshi T, Siomi H (2010) piRNA-mediated silencing in Drosophila germlines. Semin Cell Dev Biol 21:754–759

    Article  CAS  PubMed  Google Scholar 

  87. Kuramochi-Miyagawa S, Watanabe T, Gotoh K, Takamatsu K, Chuma S, Kojima-Kita K, Shiromoto Y, Asada N, Toyoda A, Fujiyama A, Totoki Y, Shibata T, Kimura T, Nakatsuji N, Noce T, Sasaki H, Nakano T (2010) MVH in piRNA processing and gene silencing of retrotransposons. Genes Dev 24:887–892

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  88. Watanabe T, Chuma S, Yamamoto Y, Kuramochi-Miyagawa S, Totoki Y, Toyoda A, Hoki Y, Fujiyama A, Shibata T, Sado T, Noce T, Nakano T, Nakatsuji N, Lin H, Sasaki H (2011) MITOPLD is a mitochondrial protein essential for nuage formation and piRNA biogenesis in the mouse germline. Dev Cell 20:364–375

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  89. Zamparini AL, Davis MY, Malone CD, Vieira E, Zavadil J, Sachidanandam R, Hannon GJ, Lehmann R (2011) Vreteno, a gonad-specific protein, is essential for germline development and primary piRNA biogenesis in Drosophila. Development 138:4039–4050

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  90. Chen C, Nott TJ, Jin J, Pawson T (2011) Deciphering arginine methylation: Tudor tells the tale. Nat Rev Mol Cell Biol 12:629–642

    Article  CAS  PubMed  Google Scholar 

  91. Vagin VV, Hannon GJ, Aravin AA (2009) Arginine methylation as a molecular signature of the Piwi small RNA pathway. Cell Cycle 8:4003–4004

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  92. Kirino Y, Kim N, de Planell-Saguer M, Khandros E, Chiorean S, Klein PS, Rigoutsos I, Jongens TA, Mourelatos Z (2009) Arginine methylation of Piwi proteins catalysed by dPRMT5 is required for Ago3 and Aub stability. Nat Cell Biol 11:652–658

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  93. Girard A, Sachidanandam R, Hannon GJ, Aravin AA (2009) Proteomic analysis of murine Piwi proteins reveals a role for arginine methylation in specifying interaction with Tudor family members. Genes Dev 23:1749–1762

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  94. Liu K, Chen C, Guo Y, Lam R, Bian C, Xu C, Zhao DY, Jin J, MacKanzie F, Pawson T, Min J (2010) Structural basis for recognition of arginine methylated Piwi proteins by the extended Tudor domain. Proc Natl Acad Sci U S A 107:18398–18403

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  95. Kirino Y, Vourekas A, Sayed N, de Lima Alves F, Thomson T, Lasko P, Rappsilber J, Jongens TA, Mourelatos Z (2010) Arginine methylation of Aubergine mediates Tudor binding and germ plasm localization. RNA 16:70–78

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  96. Vourekas A, Kirino Y, Mourelatos Z (2010) Elective affinities: a Tudor-Aubergine tale of germline partnership. Genes Dev 24:1963–1966

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  97. Patil VS, Kai T (2010) Repression of retroelements in Drosophila germline via piRNA pathway by the Tudor domain protein Tejas. Curr Biol 20:724–730

    Article  CAS  PubMed  Google Scholar 

  98. Nagao A, Sato K, Nishida KM, Siomi H, Siomi MC (2011) Gender-specific hierarchy in Nuage localization of PIWI-interacting RNA factors in Drosophila. Front Genet 2:55

    Article  PubMed Central  PubMed  Google Scholar 

  99. Ishizu H, Nagao A, Siomi H (2011) Gatekeepers for Piwi-piRNA complexes to enter the nucleus. Curr Opin Genet Dev 21:484–490

    Article  CAS  PubMed  Google Scholar 

  100. Chen C, Jin J, James DA, Adams-Cioaba MA, Park JG, Guo Y, Tenaglia E, Xu C, Gish G, Min J, Pawson T (2009) Mouse Piwi interactome identifies binding mechanism of Tdrkh Tudor domain to arginine methylated Miwi. Proc Natl Acad Sci 106:20336–20341

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  101. Siomi MC, Mannen T, Siomi H (2010) How does the royal family of Tudor rule the PIWI-interacting RNA pathway? Genes Dev 24:636–646

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  102. Shoji M, Tanaka T, Hosokawa M, Reuter M, Stark A, Kato Y, Kondoh G, Okawa K, Chujo T, Suzuki T, Hata K, Martin SL, Noce T, Kuramochi-Miyagawa S, Nakano T, Sasaki H, Pillai RS, Nakatsuji N, Chuma S (2009) The TDRD9-MIWI2 complex is essential for piRNA-mediated retrotransposon silencing in the mouse male germ line. Dev Cell 17:775–787

    Article  CAS  PubMed  Google Scholar 

  103. 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 16:639–646

    Article  CAS  PubMed  Google Scholar 

  104. Hou Y, Yuan J, Zhou X, Fu X, Cheng H, Zhou R (2012) DNA demethylation and USF regulate the meiosis-specific expression of the mouse Miwi. PLoS Genet 8:e1002716

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  105. Cerutti H, Casas-Mollano JA (2006) On the origin and functions of RNA-mediated silencing: from protists to man. Curr Genet 50:81–99

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  106. Makarova KS, Wolf YI, van der Oost J, Koonin EV (2009) Prokaryotic homologs of Argonaute proteins are predicted to function as key components of a novel system of defense against mobile genetic elements. Biol Direct 4:29

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  107. Funayama N, Nakatsukasa M, Mohri K, Masuda Y, Agata K (2010) Piwi expression in archeocytes and choanocytes in demosponges: insights into the stem cell system in demosponges. Evol Dev 12:275–287

    Article  CAS  PubMed  Google Scholar 

  108. Kerner P, Degnan SM, Marchand L, Degnan BM, Vervoort M (2011) Evolution of RNA-binding proteins in animals: insights from genome-wide analysis in the sponge Amphimedon queenslandica. Mol Biol Evol 28:2289–2303

    Article  CAS  PubMed  Google Scholar 

  109. Malone CD, Hannon GJ (2009) Molecular evolution of piRNA and transposon control pathways in Drosophila. Cold Spring Harb Symp Quant Biol 74:225–234

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  111. Carthew RW, Sontheimer EJ (2009) Origins and mechanisms of miRNAs and siRNAs. Cell 136:642–655

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  112. Olivieri D, Senti KA, 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(6):954–969

    Google Scholar 

  113. Lu J, Clark A (2010) Population dynamics of PIWI-interacting RNAs (piRNAs) and their targets in Drosophila. Genome Res 20:212–227

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  114. Castillo DM, Mell JC, Box KS, Blumenstiel JP (2011) Molecular evolution under increasing transposable element burden in Drosophila: a speed limit on the evolutionary arms race. BMC Evol Biol 11:258

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  115. Qi H, Watanabe T, Ku HY, 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 286:3789–3797

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  116. Vasileva A, Tiedau D, Firooznia A, Muller-Reichert T, Jessberger R (2009) Tdrd6 is required for spermiogenesis, chromatoid body architecture, and regulation of miRNA expression. Curr Biol 19:630–639

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  117. Morozova O, Hirst M, Marra MA (2009) Applications of new sequencing technologies for transcriptome analysis. Annu Rev Genomics Hum Genet 10:135–151

    Article  CAS  PubMed  Google Scholar 

  118. Yan Z, Hu HY, Jiang X, Maierhofer V, Neb E, He L, Hu Y, Hu H, Li N, Chen W, Khaitovich P (2011) Widespread expression of piRNA-like molecules in somatic tissues. Nucleic Acids Res 39:6596–6607

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  119. Betel D, Sheridan R, Marks DS, Sander C (2007) Computational analysis of mouse piRNA sequence and biogenesis. PLoS Comput Biol 3:e222

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  120. Lakshmi S, Agrawal S (2008) piRNABank: a web resource on classified and clustered Piwi-interacting RNAs. Nucleic Acids Res 36(Database issue):D173–D177

    Google Scholar 

  121. Zhang Y, Wang X, Kang L (2011) A k-mer scheme to predict piRNAs and characterize locust piRNAs. Bioinformatics 27:771–776

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  122. Rosenkranz D, Zischler H (2012) proTRAC – a software for probabilistic piRNA cluster detection, visualization and analysis. BMC Bioinformatics 13:5

    Google Scholar 

  123. Assis R, Kondrashov AS (2009) Rapid repetitive element-mediated expansion of piRNA clusters in mammalian evolution. Proc Natl Acad Sci U S A 106:7079–7082

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  124. Robine N, Lau NC, Balla S, Jin Z, Okamura K, Kuramochi-Miyagawa S, Blower MD, Lai EC (2009) A broadly conserved pathway generates 3′ UTR-directed primary piRNAs. Curr Biol 19:2066–2076

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  125. Kotelnikov RN, Klenov MS, Rozovsky YM, Olenina LV, Kibanov MV, Gvozdev VA (2009) Peculiarities of piRNA-mediated post-transcriptional silencing of stellate repeats in testes of Drosophila melanogaster. Nucleic Acids Res 37:3254–3263

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  126. Jensen PA, Stuart JR, Goodpaster MP, Goodman JW, Simmons MJ (2008) Cytotype regulation of P transposable elements in Drosophila melanogaster: repressor polypeptides or piRNAs? Genetics 179:1785–1793

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  127. 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 157:1364–1379

    Article  CAS  PubMed  Google Scholar 

  128. Zhang Z, Wang J, Schultz N, Shang F, Parhad SS, Tu S, Vreven T, Zamore PD, Weng Z, Theurkauf WE (2014) The HP1 homolog rhino anchors a nuclear complex that suppresses piRNA precursor splicing. Cell 157:1353–1363

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  129. Pane A, Jiang P, Zhao DY, Singh M, Schupbach T (2011) The cutoff protein regulates piRNA cluster expression and piRNA production in the Drosophila germ line. EMBO J 30:4601–4615

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  130. Huang XA, Yin H, Sweeney S, Raha D, Snyder M, Lin H (2013) A major epigenetic programming mechanism guided by piRNAs. Dev Cell 24:502–516

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  131. Ergin B (2009) Function of the mouse PIWI Proteins and biogenesis of their piRNAs in the male germline. Thesis, Duke University. http://hdl.handle.net/10161/1583

  132. Ross RJ, Weiner MM, Lin H (2014) PIWI proteins and PIWI-interacting RNAs in the soma. Nature 505:353–359

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  133. Lau NC, Ohsumi T, Borowsky M, Kingston RE, Blower MD (2009) Systematic and single cell analysis of Xenopus Piwi-interacting RNAs and Xiwi. EMBO J 28:2945–2958, Erratum in: EMBO J. 2009; 28:3458

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  134. Kolaczkowski B, Hupalo DN, Kern AD (2011) Recurrent adaptation in RNA interference genes across the Drosophila phylogeny. Mol Biol Evol 28:1033–1042

    Article  CAS  PubMed  Google Scholar 

  135. Obbard DJ, Welch JJ, Kim KW, Jiggins FM (2009) Quantifying adaptive evolution in the Drosophila immune system. PLoS Genet 5:e1000698

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  136. Lukic S, Chen K (2011) Human piRNAs are under selection in Africans and repress transposable elements. Mol Biol Evol 28:3061–3067

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  137. Ewing AD, Kazazian HH Jr (2011) Whole-genome resequencing allows detection of many rare LINE-1 insertion alleles in humans. Genome Res 21:985–990

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  138. Xiol J, Spinelli P, Laussmann MA, Homolka D, Yang Z, Cora E, Coute Y, Conn S, Kadlec J, Sachidanandam R, Kaksonen M, Cisack S, Pehrussi A, Pillai RS (2014) RNA clamping by Vasa assembles a piRNA amplifier complex on transposons transcripts. Cell 157:1696–1711

    Article  CAS  Google Scholar 

  139. Pillai RS, Chuma S (2012) piRNAs and their involvement in male germline development in mice. Dev Growth Differ 54(1):78–92

    Google Scholar 

  140. Gan H, Lin X, Zhang Z, Zhang W, Liao S, Wang L, Han C (2011) piRNA profiling during specific stages of mouse spermatogenesis. RNA 17:1191–1203

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  141. Saito K, Ishizu H, Komai M, Kotani H, Kawamura Y, Nishida KM, Siomi H, Siomi MC (2010) Roles for the Yb body components Armitage and Yb in primary piRNA biogenesis in Drosophila. Genes Dev 24:2493–2498

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  142. Pek JW, Kai T (2011) Non-coding RNAs enter mitosis: functions, conservation and implications. Cell Div 6:6

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  143. Lin H, Yin H (2008) A novel epigenetic mechanism in Drosophila somatic cells mediated by Piwi and piRNAs. Cold Spring Harb Symp Quant Biol 73:273–281

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  144. Zheng K, Xiol J, Reuter M, Eckardt S, Leu NA, McLaughlin KJ, Stark A, Sachidanandam R, Pillai RS, Wang PJ (2010) 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 107:11841–11846

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  145. Tianfang Ge D, Zamore PD (2013) Small RNA-directed silencing: the fly finds its inner fission yeast? Curr Biol 23:318–320

    Article  CAS  Google Scholar 

  146. Sigurdsson MI, Smith AV, Bjornsson HT, Jonsson JJ (2012) The distribution of a germline methylation marker suggests a regional mechanism of LINE-1 silencing by the piRNA-PIWI system. BMC Genet 13:31

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  147. Montgomery TA, Rim Y-S, Zhang C, Dowen RH, Phillips CM, Fischer SE, Ruvkun G (2012) PIWI associated siRNAs and piRNAs specifically require the Caenorhabditis elegans HEN1 ortholog henn-1. PLoS Genet 8:e1002616

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  148. Friedländer MR, Adamidi C, Han T, Lebedeva S, Isenbarger TA, Hirst M, Marra M, Nusbaum C, Lee WL, Jenkin JC, Sánchez Alvarado A, Kim JK, Rajewsky N (2009) High-resolution profiling and discovery of planarian small RNAs. Proc Natl Acad Sci U S A 106:11546–11551

    Article  PubMed Central  PubMed  Google Scholar 

  149. Gu A, Ji G, Shi X, Long Y, Xia Y, Song L, Wang S, Wang X (2010) Genetic variants in Piwi-interacting RNA pathway genes confer susceptibility to spermatogenic failure in a Chinese population. Hum Reprod 25(12):2955–2961

    Article  CAS  PubMed  Google Scholar 

  150. Angulo MA, Castro-Magana M, Sherman J, Collipp PJ, Milson J, Trunca C, Derenoncourt AN (1984) Endocrine abnormalities in a patient with partial trisomy 4q. J Med Genet 21:303–307

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  151. Sathya P, Tomkins DJ, Freeman V, Paes B, Nowaczyk MJ (1999) De novo deletion 12q: Report of a patient with 12q24.31q24.33 deletion. Am J Med Genet 84:116–119

    Article  CAS  PubMed  Google Scholar 

  152. Rizzo F, Hashim A, Marchese G, Ravo M, Tarallo R, Nassa G, Giurato G, Rinaldi A, Cordella A, Persico M, Sulas P, Perra A, Ledda-Columano GM, Columbano A, Wisz A (2014) Time regulation of p-element-induced Wimpy testis-interacting RNA exoressuib during rat liver regeneration. Hepatology. doi:10.1002/hep.27267

  153. Dyce PW, Toms D, Li J (2010) Stem cells and germ cells: microRNA and gene expression signatures. Histol Histopathol 25:505–513

    CAS  PubMed  Google Scholar 

  154. Juliano CE, Swartz SZ, Wessel GM (2010) A conserved germline multipotency program. Development 137:4113–4126

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  155. Wang Y, Liu Y, Shen X, Zhang X, Chen X, Yang C, Gao H (2012) The PIWI protein acts as a predictive marker for human gastric cancer. Int J Clin Exp Pathol 5:315–325

    PubMed Central  CAS  PubMed  Google Scholar 

  156. Cheng J, Guo JM, Xiao BX, Miao Y, Jiang Z, Zhou H, Li QN (2011) piRNA, the new non-coding RNA, is aberrantly expressed in human cancer cells. Clin Chim Acta 412:1621–1625

    Article  CAS  PubMed  Google Scholar 

  157. Alié A, Leclère L, Jager H, Dayraud C, Chang P, Le Guyader H, Quéinnec E, Manuel M (2011) Somatic stem cells express Piwi and Vasa genes in an adult ctenophore: ancient association of “germ line genes” with stemness. Dev Biol 350:183–197

    Article  PubMed  CAS  Google Scholar 

  158. Hashimoto H, Sudo T, Mikami Y, Otani M, Takano M, Tsuda H, Itamochi H, Katabuchi H, Ito M, Nishimura R (2008) Germ cell specific protein VASA is over-expressed in epithelial ovarian cancer and disrupts DNA damage-induced G2 checkpoint. Gynecol Oncol 111:312–319

    Article  CAS  PubMed  Google Scholar 

  159. Siddiqi S, Matushansky I (2012) Piwis and piwi-interacting RNAs in the epigenetics of cancer. J Cell Biochem 113:373–380

    Article  CAS  PubMed  Google Scholar 

  160. Siddiqi S, Terry M, Matushansky I (2012) Hiwi mediated tumorigenesis is associated with DNA hypermethylation. PLoS One 7:e33711

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  161. Chen L, Shen R, Ye Y, Pu XA, Liu X, Duan W, Wen J, Zimmerer J, Wang Y, Liu Y, Lasky LC, Heerema NA, Perrotti D, Ozato K, Kuramochi-Miyagawa S, Nakano T, Yates AJ, Carson WE 3rd, Lin H, Barsky SH, Gao JX (2007) Precancerous stem cells have the potential for both benign and malignant differentiation. PLoS One 2:e293

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  162. Fereira HJ, Heyn H, Garcia del Muro X, Vidal A, Larriba S, Munoz C, Villanueva A, Esteller M (2014) Epigenetic loss of the PIWI/piRNA machinery in human testicular tumorigenesis. Epigenetics 9:113–118

    Article  CAS  Google Scholar 

  163. Rouget C, Papin C, Boureux A, Meunier AC, Franco B, Robine N, Lai EC, Pelisson A, Simonelig M (2010) Maternal mRNA deadenylation and decay by the piRNA pathway in the early Drosophila embryo. Nature 467:1128–1132

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  164. Shpiz S, Olovnikov I, Sergeeva A, Lavrov S, Abramov Y, Savitsky M, Kalmykova A (2011) Mechanism of the piRNA-mediated silencing of Drosophila telomeric retrotransposons. Nucleic Acids Res 39:8703–8711

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  165. Lee E, Banerjee S, Zhou H, Jammalamadaka A, Arcila M, Manjunath BS, Kosik KS (2011) Identification of piRNAs in the central nervous system. RNA 17:1090–1099

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  166. Esposito T, Magliocca S, Formicola D, Gianfrancesco F (2011) piR_015520 belongs to Piwi-associated RNAs regulates expression of the human melatonin receptor 1A gene. PLoS One 6(7):e22727

    Google Scholar 

  167. Rajasethupathy P, Antonov I, Sheridan R, Frey S, Sander C, Tuschl T, Kandel ER (2012) A role for neuronal piRNAs in the epigenetic control of memory-related synaptic plasticity. Cell 149:693–707

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  168. Mendzabal JA, Llamazares S, Rossell D, Gonzalez C (2010) Ectopic expression of germline genes drives malignant brain tumor growth in Drosophila. Science 330:1824–1827

    Google Scholar 

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Demoliou, C. (2015). piRNAs-Transposon Silencing and Germ Line Development. In: Felekkis, K., Voskarides, K. (eds) Genomic Elements in Health, Disease and Evolution. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-3070-8_3

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