A piece of the pi(e): The diverse roles of animal piRNAs and their PIWI partners

Seminars in Cell and Developmental Biology

Volumn 47-48, Issue , 2015, Pages 17-31

  Lim, Robyn S M ^a,c   Kai, Toshie ^a,b  

^a NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^b OSAKA UNIVERSITY   (Japan)

^c SINGAPORE GENERAL HOSPITAL   (Singapore)

Author keywords

Evolutionary conservation; Gene regulation; PiRNA biogenesis; PIWI protein; PIWI interacting RNA (piRNA); Transposable elements

Indexed keywords

PIWI INTERACTING RNA; PIWI PROTEIN; ARGONAUTE PROTEIN; PIWIL1 PROTEIN, HUMAN; PROTEIN BINDING; SMALL INTERFERING RNA; TRANSPOSON;

ARTICLE; BIOGENESIS; EMBRYO DEVELOPMENT; EPIGENETICS; GENOME; GERMLINE STEM CELL; GONAD; HUMAN; MOLECULAR BIOLOGY; NEOPLASM; NERVE CELL; NONHUMAN; PROTEIN FUNCTION; REGENERATION; REGENERATIVE ABILITY; RNA TRANSCRIPTION; SOMATIC CELL; STEM CELL; TRANSPOSON; ANIMAL; CLASSIFICATION; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; MOLECULAR EVOLUTION; PHYLOGENY; SIGNAL TRANSDUCTION;

ANIMALS; ARGONAUTE PROTEINS; DNA TRANSPOSABLE ELEMENTS; EMBRYONIC DEVELOPMENT; EVOLUTION, MOLECULAR; GENE EXPRESSION REGULATION, DEVELOPMENTAL; PHYLOGENY; PROTEIN BINDING; RNA, SMALL INTERFERING; SIGNAL TRANSDUCTION;

EID: 84952045489     PISSN: 10849521     EISSN: 10963634     Source Type: Journal    
DOI: 10.1016/j.semcdb.2015.10.025     Document Type: Article

References (308)

1. Cerutti H., Casas-Mollano J.A. On the origin and functions of RNA-mediated silencing: from protists to man. Curr. Genet. 2006, 50:81-99. 10.1007/s00294-006-0078-x.
2. Makarova K.S., Wolf Y.I., van der Oost J., Koonin E.V. Prokaryotic homologs of Argonaute proteins are predicted to function as key components of a novel system of defense against mobile genetic elements. Biol Direct. 2009, 4:29. 10.1186/1745-6150-4-29.
3. Mourelatos Z., Dostie J., Paushkin S., Sharma A., Charroux B., Abel L., et al. miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs. Genes Dev. 2002, 16:720-728. 10.1101/gad.974702.
4. Czech B., Malone C.D., Zhou R., Stark A., Schlingeheyde C., Dus M., et al. An endogenous small interfering RNA pathway in Drosophila. Nature 2008, 453:798-802. 10.1038/nature07007.
5. Kawamura Y., Saito K., Kin T., Ono Y., Asai K., Sunohara T., et al. Drosophila endogenous small RNAs bind to Argonaute 2 in somatic cells. Nature 2008, 453:793-797. 10.1038/nature06938.
6. Watanabe T., Totoki Y., Toyoda A., Kaneda M., Kuramochi-Miyagawa S., Obata Y., et al. Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes. Nature 2008, 453:539-543. 10.1038/nature06908.
7. Lee R.C., Ambros V. An extensive class of small RNAs in Caenorhabditis elegans. Science 2001, 294:862-864. 10.1126/science.1065329.
8. Lau N.C., Lim L.P., Weinstein E.G., Bartel D.P. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 2001, 294:858-862. 10.1126/science.1065062.
9. Lagos-Quintana M., Rauhut R., Lendeckel W., Tuschl T. Identification of novel genes coding for small expressed RNAs. Science 2001, 294:853-858. 10.1126/science.1064921.
10. Reinhart B.J., Weinstein E.G., Rhoades M.W., Bartel B., Bartel D.P. MicroRNAs in plants. Genes Dev. 2002, 16:1616-1626. 10.1101/gad.1004402.
11. Xie Z., Johansen L.K., Gustafson A.M., Kasschau K.D., Lellis A.D., Zilberman D., et al. Genetic and functional diversification of small RNA pathways in plants. PLoS Biol. 2004, 2:E104. 10.1371/journal.pbio.0020104.
12. Llave C., Kasschau K.D., Rector M.A., Carrington J.C. Endogenous and silencing-associated small RNAs in plants. Plant Cell 2002, 14:1605-1619.
13. Denli A.M., Tops B.B.J., Plasterk R.H.A., Ketting R.F., Hannon G.J. Processing of primary microRNAs by the Microprocessor complex. Nature 2004, 432:231-235. 10.1038/nature03049.
14. Lee Y., Ahn C., Han J., Choi H., Kim J., Yim J., et al. The nuclear RNase III Drosha initiates microRNA processing. Nature 2003, 425:415-419. 10.1038/nature01957.
15. Ghildiyal M., Seitz H., Horwich M.D., Li C., Du T., Lee S., et al. Endogenous siRNAs derived from transposons and mRNAs in Drosophila somatic cells. Science 2008, 320:1077-1081. 10.1126/science.1157396.
16. Okamura K., Balla S., Martin R., Liu N., Lai E.C. Two distinct mechanisms generate endogenous siRNAs from bidirectional transcription in Drosophila melanogaster. Nat. Struct. Mol. Biol. 2008, 15:581-590. 10.1038/nsmb.1438.
17. Okamura K., Chung W.-J., Ruby J.G., Guo H., Bartel D.P., Lai E.C. The Drosophila hairpin RNA pathway generates endogenous short interfering RNAs. Nature 2008, 453:803-806. 10.1038/nature07015.
18. Tam O.H., Aravin A.A., Stein P., Girard A., Murchison E.P., Cheloufi S., et al. Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes. Nature 2008, 453:534-538. 10.1038/nature06904.
19. Ambros V., Lee R.C., Lavanway A., Williams P.T., Jewell D. MicroRNAs and other tiny endogenous RNAs in C. elegans. Curr. Biol. 2003, 13:807-818.
20. Ketting R.F., Fischer S.E., Bernstein E., Sijen T., Hannon G.J., Plasterk R.H. Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes Dev. 2001, 15:2654-2659. 10.1101/gad.927801.
21. Hutvágner G., McLachlan J., Pasquinelli A.E., Bálint E., Tuschl T., Zamore P.D. A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science 2001, 293:834-838. 10.1126/science.1062961.
22. Bernstein E., Caudy A.A., Hammond S.M., Hannon G.J. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 2001, 409:363-366. 10.1038/35053110.
23. Knight S.W., Bass B.L. A role for the RNase III enzyme DCR-1 in RNA interference and germ line development in Caenorhabditis elegans. Science 2001, 293:2269-2271. 10.1126/science.1062039.
24. Bagga S., Bracht J., Hunter S., Massirer K., Holtz J., Eachus R., et al. Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation. Cell 2005, 122:553-563. 10.1016/j.cell.2005.07.031.
25. Jing Q., Huang S., Guth S., Zarubin T., Motoyama A., Chen J., et al. Involvement of microRNA in AU-rich element-mediated mRNA instability. Cell 2005, 120:623-634. 10.1016/j.cell.2004.12.038.
26. Lim L.P., Lau N.C., Garrett-Engele P., Grimson A., Schelter J.M., Castle J., et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 2005, 433:769-773. 10.1038/nature03315.
27. Giraldez A.J., Mishima Y., Rihel J., Grocock R.J., Van Dongen S., Inoue K., et al. Zebrafish MiR-430 promotes deadenylation and clearance of maternal mRNAs. Science 2006, 312:75-79. 10.1126/science.1122689.
28. Rehwinkel J., Natalin P., Stark A., Brennecke J., Cohen S.M., Izaurralde E. Genome-wide analysis of mRNAs regulated by Drosha and Argonaute proteins in Drosophila melanogaster. Mol. Cell. Biol. 2006, 26:2965-2975. 10.1128/MCB.26.8.2965-2975.2006.
29. Wu L., Fan J., Belasco J.G. MicroRNAs direct rapid deadenylation of mRNA. Proc. Natl. Acad. Sci. U. S. A. 2006, 103:4034-4039. 10.1073/pnas.0510928103.
30. Baek D., Villén J., Shin C., Camargo F.D., Gygi S.P., Bartel D.P. The impact of microRNAs on protein output. Nature 2008, 455:64-71. 10.1038/nature07242.
31. Selbach M., Schwanhäusser B., Thierfelder N., Fang Z., Khanin R., Rajewsky N. Widespread changes in protein synthesis induced by microRNAs. Nature 2008, 455:58-63. 10.1038/nature07228.
32. Guo H., Ingolia N.T., Weissman J.S., Bartel D.P. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature 2010, 466:835-840. 10.1038/nature09267.
33. Vasudevan S., Tong Y., Steitz J.A. Switching from repression to activation: microRNAs can up-regulate translation. Science 2007, 318:1931-1934. 10.1126/science.1149460.
34. Li L.-C., Okino S.T., Zhao H., Pookot D., Place R.F., Urakami S., et al. Small dsRNAs induce transcriptional activation in human cells. Proc. Natl. Acad. Sci. U. S. A. 2006, 103:17337-17342. 10.1073/pnas.0607015103.
35. Janowski B.A., Younger S.T., Hardy D.B., Ram R., Huffman K.E., Corey D.R. Activating gene expression in mammalian cells with promoter-targeted duplex RNAs. Nat. Chem. Biol. 2007, 3:166-173. 10.1038/nchembio860.
36. Huang V., Qin Y., Wang J., Wang X., Place R.F., Lin G., et al. RNAa is conserved in mammalian cells. PLoS ONE 2010, 5:e8848. 10.1371/journal.pone.0008848.
37. Seth M., Shirayama M., Gu W., Ishidate T., Conte D., Mello C.C. The C. elegans CSR-1 argonaute pathway counteracts epigenetic silencing to promote germline gene expression. Dev. Cell 2013, 27:656-663. 10.1016/j.devcel.2013.11.014.
38. Turner M., Jiao A., Slack F.J. Autoregulation of lin-4 microRNA transcription by RNA activation (RNAa) in C. elegans. Cell Cycle 2014, 13:772-781. 10.4161/cc.27679.
39. Ha M., Kim V.N. Regulation of microRNA biogenesis. Nat. Rev. Mol. Cell Biol. 2014, 15:509-524. 10.1038/nrm3838.
40. Bartel D.P. MicroRNAs: target recognition and regulatory functions. Cell 2009, 136:215-233. 10.1016/j.cell.2009.01.002.
41. Claycomb J.M. Ancient endo-siRNA pathways reveal new tricks. Curr. Biol. 2014, 24:R703-R715. 10.1016/j.cub.2014.06.009.
42. Okamura K., Lai E.C. Endogenous small interfering RNAs in animals. Nat. Rev. Mol. Cell Biol. 2008, 9:673-678. 10.1038/nrm2479.
43. Ameres S.L., Zamore P.D. Diversifying microRNA sequence and function. Nat. Rev. Mol. Cell Biol. 2013, 14:475-488. 10.1038/nrm3611.
44. Jinek M., Doudna J. A three-dimensional view of the molecular machinery of RNA interference. Nature 2009, 457:405-412. 10.1038/nature07755.
45. Siomi H., Siomi M.C. On the road to reading the RNA-interference code. Nature 2009, 457:396-404. 10.1038/nature07754.
46. Yang J.-S., Lai E.C. Alternative miRNA biogenesis pathways and the interpretation of core miRNA pathway mutants. Mol. Cell 2011, 43:892-903. 10.1016/j.molcel.2011.07.024.
47. Chak L.-L., Okamura K. Argonaute-dependent small RNAs derived from single-stranded, non-structured precursors. Front. Genet. 2014, 5:172. 10.3389/fgene.2014.00172.
48. Okamura K. Diversity of animal small RNA pathways and their biological utility. Wiley Interdiscip. Rev. RNA 2012, 3:351-368. 10.1002/wrna.113.
49. Aravin A.A., Lagos-Quintana M., Yalcin A., Zavolan M., Marks D., Snyder B., et al. The small RNA profile during Drosophila melanogaster development. Dev. Cell 2003, 5:337-350.
50. Vagin V.V., Sigova A., Li C., Seitz H., Gvozdev V., Zamore P.D. A distinct small RNA pathway silences selfish genetic elements in the germline. Science 2006, 313:320-324. 10.1126/science.1129333.
51. Grivna S.T., Beyret E., Wang Z., Lin H. A novel class of small RNAs in mouse spermatogenic cells. Genes Dev. 2006, 20:1709-1714. 10.1101/gad.1434406.
52. Houwing S., Kamminga L.M., Berezikov E., Cronembold D., Girard A., van den Elst H., et al. A role for Piwi and piRNAs in germ cell maintenance and transposon silencing in Zebrafish. Cell 2007, 129:69-82. 10.1016/j.cell.2007.03.026.
53. Gunawardane L.S., Saito K., Nishida K.M., Miyoshi K., Kawamura Y., Nagami T., et al. A slicer-mediated mechanism for repeat-associated siRNA 5' end formation in Drosophila. Science 2007, 315:1587-1590. 10.1126/science.1140494.
54. Saito K., Nishida K.M., Mori T., Kawamura Y., Miyoshi K., Nagami T., et al. Specific association of Piwi with rasiRNAs derived from retrotransposon and heterochromatic regions in the Drosophila genome. Genes Dev. 2006, 20:2214-2222. 10.1101/gad.1454806.
55. Aravin A.A., Hannon G.J., Brennecke J. The Piwi-piRNA pathway provides an adaptive defense in the transposon arms race. Science 2007, 318:761-764. 10.1126/science.1146484.
56. Brennecke J., Aravin A., Stark A., Dus M. Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila. Cell 2007, 128:1089-1103. 10.1016/j.cell.2007.01.043.
57. Lau N.C., Seto A.G., Kim J., Kuramochi-Miyagawa S., Nakano T., Bartel D.P., et al. Characterization of the piRNA complex from rat testes. Science 2006, 313:363-367. 10.1126/science.1130164.
58. Lin H., Spradling A.C. A novel group of pumilio mutations affects the asymmetric division of germline stem cells in the Drosophila ovary. Development 1997, 124:2463-2476.
59. Carmell M.A., Xuan Z., Zhang M.Q., Hannon G.J. The Argonaute family: tentacles that reach into RNAi, developmental control, stem cell maintenance, and tumorigenesis. Genes Dev. 2002, 16:2733-2742. 10.1101/gad.1026102.
60. Li C., Vagin V.V., Lee S., Xu J., Ma S., Xi H., et al. Collapse of germline piRNAs in the absence of Argonaute3 reveals somatic piRNAs in flies. Cell 2009, 137:509-521. 10.1016/j.cell.2009.04.027.
61. Malone C.D., Brennecke J., Dus M., Stark A., McCombie W.R., Sachidanandam R., et al. Specialized piRNA pathways act in germline and somatic tissues of the Drosophila ovary. Cell 2009, 137:522-535. 10.1016/j.cell.2009.03.040.
62. Slotkin R.K., Martienssen R. Transposable elements and the epigenetic regulation of the genome. Nat. Rev. Genet. 2007, 8:272-285. 10.1038/nrg2072.
63. Klattenhoff C., Theurkauf W. Biogenesis and germline functions of piRNAs. Development 2008, 135:3-9. 10.1242/dev.006486.
64. Mochizuki K., Fine N.A., Fujisawa T., Gorovsky M.A. Analysis of a piwi-related gene implicates small RNAs in genome rearrangement in Tetrahymena. Cell 2002, 110:689-699. 10.1016/S0092-8674(02)00909-1.
65. Mochizuki K., Gorovsky M.A. Conjugation-specific small RNAs in Tetrahymena have predicted properties of scan (scn) RNAs involved in genome rearrangement. Genes Dev. 2004, 18:2068-2073. 10.1101/gad.1219904.
66. Aronica L., Bednenko J., Noto T., DeSouza L.V., Siu K.W.M., Loidl J., et al. Study of an RNA helicase implicates small RNA-noncoding RNA interactions in programmed DNA elimination in Tetrahymena. Genes Dev. 2008, 22:2228-2241. 10.1101/gad.481908.
67. Fang W., Wang X., Bracht J.R., Nowacki M., Landweber L.F. Piwi-interacting RNAs protect DNA against loss during Oxytricha genome rearrangement. Cell 2012, 151:1243-1255. 10.1016/j.cell.2012.10.045.
68. Schoeberl U.E., Mochizuki K. Keeping the soma free of transposons: programmed DNA elimination in ciliates. J. Biol. Chem. 2011, 286:37045-37052. 10.1074/jbc.R111.276964.
69. Mochizuki K. Developmentally programmed, RNA-directed genome rearrangement in Tetrahymena. Dev. Growth Differ. 2012, 54:108-119. 10.1111/j.1440-169X.2011.01305.x.
70. Kataoka K., Mochizuki K. RNA infrastructure and networks 2011, vol. 722. Springer, New York, NY. 10.1007/978-1-4614-0332-6.
71. Mochizuki K., Gorovsky M.A. A Dicer-like protein in Tetrahymena has distinct functions in genome rearrangement, chromosome segregation, and meiotic prophase. Genes Dev. 2005, 19:77-89. 10.1101/gad.1265105.
72. Yao M.-C. Programmed DNA deletion as an RNA-guided system of genome defense. Science 2003, 300(80-):1581-1584. 10.1126/science.1084737.
73. Anand A., Kai T. The tudor domain protein kumo is required to assemble the nuage and to generate germline piRNAs in Drosophila. EMBO J. 2012, 31:870-882. 10.1038/emboj.2011.449.
74. Carmell M.A., Girard A., van de Kant H.J.G., Bourc'his D., Bestor T.H., de Rooij D.G., et al. MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline. Dev. Cell 2007, 12:503-514. 10.1016/j.devcel.2007.03.001.
75. Deng W., Lin H. miwi, a murine homolog of piwi, encodes a cytoplasmic protein essential for spermatogenesis. Dev. Cell 2002, 2:819-830.
76. Handler D., Olivieri D., Novatchkova M., Gruber F.S., Meixner K., Mechtler K., et al. A systematic analysis of Drosophila TUDOR domain-containing proteins identifies Vreteno and the Tdrd12 family as essential primary piRNA pathway factors. EMBO J. 2011, 30:3977-3993. 10.1038/emboj.2011.308.
77. Houwing S., Berezikov E., Ketting R.F. Zili is required for germ cell differentiation and meiosis in zebrafish. EMBO J. 2008, 27:2702-2711. 10.1038/emboj.2008.204.
78. Kuramochi-Miyagawa S., Kimura T., Ijiri T.W., Isobe T., Asada N., Fujita Y., et al. Mili, a mammalian member of piwi family gene, is essential for spermatogenesis. Development 2004, 131:839-849. 10.1242/dev.00973.
79. Lim A.K., Kai T. Unique germ-line organelle, nuage, functions to repress selfish genetic elements in Drosophila melanogaster. Proc. Natl. Acad. Sci. U.S.A. 2007, 104:6714-6719. 10.1073/pnas.0701920104.
80. Pane A., Jiang P., Zhao D.Y., Singh M., Schüpbach T. The Cutoff protein regulates piRNA cluster expression and piRNA production in the Drosophila germline. EMBO J. 2011, 30:4601-4615. 10.1038/emboj.2011.334.
81. Patil V.S., Kai T. Repression of retroelements in Drosophila germline via piRNA pathway by the Tudor domain protein Tejas. Curr. Biol. 2010, 20:724-730. 10.1016/j.cub.2010.02.046.
82. Xiol J., Cora E., Koglgruber R., Chuma S., Subramanian S., Hosokawa M., et al. A role for Fkbp6 and the chaperone machinery in piRNA amplification and transposon silencing. Mol. Cell 2012, 47:970-979. 10.1016/j.molcel.2012.07.019.
83. Zhang Z., Xu J., Koppetsch B.S., Wang J., Tipping C., Ma S., et al. Heterotypic piRNA ping-pong requires Qin, a protein with both E3 ligase and Tudor domains. Mol. Cell 2011, 44:572-584. 10.1016/j.molcel.2011.10.011.
84. Klattenhoff C., Bratu D.P., McGinnis-Schultz N., Koppetsch B.S., Cook H.A., Theurkauf W.E. Drosophila rasiRNA pathway mutations disrupt embryonic axis specification through activation of an ATR/Chk2 DNA damage response. Dev. Cell 2007, 12:45-55. 10.1016/j.devcel.2006.12.001.
85. Chen Y., Pane A., Schüpbach T. Cutoff and aubergine mutations result in retrotransposon upregulation and checkpoint activation in Drosophila. Curr. Biol. 2007, 17:637-642. 10.1016/j.cub.2007.02.027.
86. al-Mukhtar K.A., Webb A.C. An ultrastructural study of primordial germ cells, oogonia and early oocytes in Xenopus laevis. J. Embryol. Exp. Morphol. 1971, 26:195-217.
87. Eddy E.M. Fine structural observations on the form and distribution of nuage in germ cells of the rat. Anat. Rec. 1974, 178:731-757. 10.1002/ar.1091780406.
88. Mahowald A.P. Polar granules of Drosophila. II. Ultrastructural changes during early embryogenesis. J. Exp. Zool. 1968, 167:237-261. 10.1002/jez.1401670211.
89. Wang J., Saxe J.P., Tanaka T., Chuma S., Lin H. Mili interacts with Tudor domain-containing protein 1 in regulating spermatogenesis. Curr. Biol. 2009, 19:640-644. 10.1016/j.cub.2009.02.061.
90. Eddy E.M. Germ plasm and the differentiation of the germ cell line. Int. Rev. Cytol. 1975, 43:229-280.
91. Extavour C.G.M. Evolution of the bilaterian germ line: lineage origin and modulation of specification mechanisms. Integr. Comp. Biol. 2007, 47:770-785. 10.1093/icb/icm027.
92. Voronina E., Seydoux G., Sassone-Corsi P., Nagamori I. RNA granules in germ cells. Cold Spring Harb. Perspect. Biol. 2011, 3:a002774. 10.1101/cshperspect.a002774.
93. Watanabe T., Chuma S., Yamamoto Y., Kuramochi-Miyagawa S., Totoki Y., Toyoda A., et al. MITOPLD is a mitochondrial protein essential for nuage formation and piRNA biogenesis in the mouse germline. Dev. Cell 2011, 20:364-375. 10.1016/j.devcel.2011.01.005.
94. Huang H., Gao Q., Peng X., Choi S.-Y., Sarma K., Ren H., et al. piRNA-associated germline nuage formation and spermatogenesis require MitoPLD profusogenic mitochondrial-surface lipid signaling. Dev. Cell 2011, 20:376-387. 10.1016/j.devcel.2011.01.004.
95. Saxe J.P., Chen M., Zhao H., Lin H. Tdrkh is essential for spermatogenesis and participates in primary piRNA biogenesis in the germline. EMBO J. 2013, 32:1869-1885. 10.1038/emboj.2013.121.
96. Aravin A.A., Chan D.C. piRNAs meet mitochondria. Dev. Cell 2011, 20:287-288. 10.1016/j.devcel.2011.03.003.
97. Mohn F., Sienski G., Handler D., Brennecke J. The rhino-deadlock-cutoff complex licenses noncanonical transcription of dual-strand piRNA clusters in Drosophila. Cell 2014, 157:1364-1379. 10.1016/j.cell.2014.04.031.
98. Aravin A., Gaidatzis D., Pfeffer S., Lagos-Quintana M., Landgraf P., Iovino N., et al. A novel class of small RNAs bind to MILI protein in mouse testes. Nature 2006, 442:203-207. 10.1038/nature04916.
99. Girard A., Sachidanandam R., Hannon G.J., Carmell M.A. A germline-specific class of small RNAs binds mammalian Piwi proteins. Nature 2006, 442:199-202. 10.1038/nature04917.
100. Li X.Z., Roy C.K., Dong X., Bolcun-Filas E., Wang J., Han B.W., et al. An ancient transcription factor initiates the burst of piRNA production during early meiosis in mouse testes. Mol. Cell 2013, 50:67-81. 10.1016/j.molcel.2013.02.016.
101. Ha H., Song J., Wang S., Kapusta A., Feschotte C., Chen K.C., et al. A comprehensive analysis of piRNAs from adult human testis and their relationship with genes and mobile elements. BMC Genomics 2014, 15:545. 10.1186/1471-2164-15-545.
102. Murchison E.P., Kheradpour P., Sachidanandam R., Smith C., Hodges E., Xuan Z., et al. Conservation of small RNA pathways in platypus. Genome Res. 2008, 18:995-1004. 10.1101/gr.073056.107.
103. Lau N.C., Ohsumi T., Borowsky M., Kingston R.E., Blower M.D. Systematic and single cell analysis of Xenopus Piwi-interacting RNAs and Xiwi. EMBO J. 2009, 28:2945-2958. 10.1038/emboj.2009.237.
104. Armisen J., Gilchrist M.J., Wilczynska A., Standart N., Miska E.A. Abundant and dynamically expressed miRNAs, piRNAs, and other small RNAs in the vertebrate Xenopus tropicalis. Genome Res. 2009, 19:1766-1775. 10.1101/gr.093054.109.
105. Friedländer M.R., Adamidi C., Han T., Lebedeva S., Isenbarger T.A., Hirst M., et al. High-resolution profiling and discovery of planarian small RNAs. Proc. Natl. Acad. Sci. U. S. A. 2009, 106:11546-11551. 10.1073/pnas.0905222106.
106. Krishna S., Nair A., Cheedipudi S., Poduval D., Dhawan J., Palakodeti D., et al. Deep sequencing reveals unique small RNA repertoire that is regulated during head regeneration in Hydra magnipapillata. Nucleic Acids Res. 2013, 41:599-616. 10.1093/nar/gks1020.
107. Lim R.S.M., Anand A., Nishimiya-Fujisawa C., Kobayashi S., Kai T. Analysis of Hydra PIWI proteins and piRNAs uncover early evolutionary origins of the piRNA pathway. Dev. Biol. 2014, 386:237-251.
108. Grimson A., Srivastava M., Fahey B., Woodcroft B.J., Chiang H.R., King N., et al. Early origins and evolution of microRNAs and Piwi-interacting RNAs in animals. Nature 2008, 455:1193-1197. 10.1038/nature07415.
109. Zhang Z., Wang J., Schultz N., Zhang F., Parhad S.S., Tu S., et al. The HP1 homolog rhino anchors a nuclear complex that suppresses piRNA precursor splicing. Cell 2014, 157:1353-1363. 10.1016/j.cell.2014.04.030.
110. St Pierre S.E., Ponting L., Stefancsik R., McQuilton P. FlyBase 102-advanced approaches to interrogating FlyBase. Nucleic Acids Res. 2014, 42:D780-D788. 10.1093/nar/gkt1092.
111. Cecere G., Zheng G.X.Y., Mansisidor A.R., Klymko K.E., Grishok A. Promoters recognized by forkhead proteins exist for individual 21U-RNAs. Mol. Cell 2012, 47:734-745. 10.1016/j.molcel.2012.06.021.
112. Robine N., Lau N.C., Balla S., Jin Z., Okamura K., Kuramochi-Miyagawa S., et al. A broadly conserved pathway generates 3'UTR-directed primary piRNAs. Curr. Biol. 2009, 19:2066-2076. 10.1016/j.cub.2009.11.064.
113. Zhang F., Wang J., Xu J., Zhang Z., Koppetsch B.S., Schultz N., et al. UAP56 couples piRNA clusters to the perinuclear transposon silencing machinery. Cell 2012, 151:871-884. 10.1016/j.cell.2012.09.040.
114. Saito K., Ishizu H., Komai M., Kotani H., Kawamura Y., Nishida K.M., et al. Roles for the Yb body components Armitage and Yb in primary piRNA biogenesis in Drosophila. Genes Dev. 2010, 24:2493-2498. 10.1101/gad.1989510.
115. Vourekas A., Zheng K., Fu Q., Maragkakis M., Alexiou P., Ma J., et al. The RNA helicase MOV10L1 binds piRNA precursors to initiate piRNA processing. Genes Dev. 2015, 10.1101/gad.254631.114.
116. Pane A., Wehr K., Schüpbach T. Zucchini and squash encode two putative nucleases required for rasiRNA production in the Drosophila germline. Dev. Cell 2007, 12:851-862. 10.1016/j.devcel.2007.03.022.
117. Ipsaro J.J., Haase A.D., Knott S.R., Joshua-Tor L., Hannon G.J. The structural biochemistry of Zucchini implicates it as a nuclease in piRNA biogenesis. Nature 2012, 491:279-283. 10.1038/nature11502.
118. Nishimasu H., Ishizu H., Saito K., Fukuhara S., Kamatani M.K., Bonnefond L., et al. Structure and function of Zucchini endoribonuclease in piRNA biogenesis. Nature 2012, 491:284-287. 10.1038/nature11509.
119. Voigt F., Reuter M., Kasaruho A., Schulz E.C., Pillai R.S., Barabas O. Crystal structure of the primary piRNA biogenesis factor Zucchini reveals similarity to the bacterial PLD endonuclease Nuc. RNA 2012, 18:2128-2134. 10.1261/rna.034967.112.
120. Kawaoka S., Izumi N., Katsuma S., Tomari Y. 3' end formation of PIWI-interacting RNAs in vitro. Mol. Cell 2011, 43:1015-1022. 10.1016/j.molcel.2011.07.029.
121. Feltzin V.L., Khaladkar M., Abe M., Parisi M., Hendriks G.-J., Kim J., et al. The exonuclease Nibbler regulates age-associated traits and modulates piRNA length in Drosophila. Aging Cell 2015, 10.1111/acel.12323.
122. Juliano C.E., Reich A., Liu N., Götzfried J., Zhong M., Uman S., et al. PIWI proteins and PIWI-interacting RNAs function in Hydra somatic stem cells. Proc. Natl. Acad. Sci. U. S. A. 2014, 111:337-342. 10.1073/pnas.1320965111.
123. Aravin A.A., Sachidanandam R., Bourc'his D., Schaefer C., Pezic D., Toth K.F., et al. A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice. Mol. Cell 2008, 31:785-799. 10.1016/j.molcel.2008.09.003.
124. Houwing S., Berezikov E., Ketting R.F. Zili is required for germ cell differentiation and meiosis in zebrafish. EMBO J. 2008, 27:2702-2711. 10.1038/emboj.2008.204.
125. Horwich M.D., Li C., Matranga C., Vagin V., Farley G., Wang P., et al. The Drosophila RNA methyltransferase, DmHen1, modifies germline piRNAs and single-stranded siRNAs in RISC. Curr. Biol. 2007, 17:1265-1272. 10.1016/j.cub.2007.06.030.
126. Kirino Y., Mourelatos Z. The mouse homolog of HEN1 is a potential methylase for Piwi-interacting RNAs. RNA 2007, 13:1397-1401. 10.1261/rna.659307.
127. Ohara T., Sakaguchi Y., Suzuki T., Ueda H., Miyauchi K., Suzuki T. The 3' termini of mouse Piwi-interacting RNAs are 2'-O-methylated. Nat. Struct. Mol. Biol. 2007, 14:349-350. 10.1038/nsmb1220.
128. Saito K., Sakaguchi Y., Suzuki T., Suzuki T., Siomi H., Siomi M.C. Pimet, the Drosophila homolog of HEN1, mediates 2'-O-methylation of Piwi-interacting RNAs at their 3' ends. Genes Dev. 2007, 21:1603-1608. 10.1101/gad.1563607.
129. Kamminga L.M., Luteijn M.J., den Broeder M.J., Redl S., Kaaij L.J.T., Roovers E.F., et al. Hen1 is required for oocyte development and piRNA stability in zebrafish. EMBO J. 2010, 29:3688-3700. 10.1038/emboj.2010.233.
130. Montgomery T.A., Rim Y.-S., Zhang C., Dowen R.H., Phillips C.M., Fischer S.E.J., et al. PIWI associated siRNAs and piRNAs specifically require the Caenorhabditis elegans HEN1 ortholog henn-1. PLoS Genet. 2012, 8:e1002616. 10.1371/journal.pgen.1002616.
131. Billi A.C., Alessi A.F., Khivansara V., Han T., Freeberg M., Mitani S., et al. The Caenorhabditis elegans HEN1 ortholog, HENN-1, methylates and stabilizes select subclasses of germline small RNAs. PLoS Genet. 2012, 8:e1002617. 10.1371/journal.pgen.1002617.
132. Kamminga L.M., van Wolfswinkel J.C., Luteijn M.J., Kaaij L.J.T., Bagijn M.P., Sapetschnig A., et al. Differential impact of the HEN1 homolog HENN-1 on 21U and 26G RNAs in the germline of Caenorhabditis elegans. PLoS Genet. 2012, 8:e1002702. 10.1371/journal.pgen.1002702.
133. Shao P., Liao J.-Y., Guan D.-G., Yang J.-H., Zheng L.-L., Jing Q., et al. Drastic expression change of transposon-derived piRNA-like RNAs and microRNAs in early stages of chicken embryos implies a role in gastrulation. RNA Biol. 2012, 9:212-227. 10.4161/rna.18489.
134. Tian Y., Simanshu D.K., Ma J.-B., Patel D.J. Structural basis for piRNA 2'-O-methylated 3'-end recognition by Piwi PAZ (Piwi/Argonaute/Zwille) domains. Proc. Natl. Acad. Sci. U. S. A. 2011, 108:903-910. 10.1073/pnas.1017762108.
135. Shen B., Goodman H.M. Uridine addition after microRNA-directed cleavage. Science 2004, 306:997. 10.1126/science.1103521.
136. Van Wolfswinkel J.C., Claycomb J.M., Batista P.J., Mello C.C., Berezikov E., Ketting R.F. CDE-1 affects chromosome segregation through uridylation of CSR-1-bound siRNAs. Cell 2009, 139:135-148. 10.1016/j.cell.2009.09.012.
137. Ibrahim F., Rymarquis L.A., Kim E.-J., Becker J., Balassa E., Green P.J., et al. Uridylation of mature miRNAs and siRNAs by the MUT68 nucleotidyltransferase promotes their degradation in Chlamydomonas. Proc. Natl. Acad. Sci. U. S. A. 2010, 107:3906-3911. 10.1073/pnas.0912632107.
138. Ameres S.L., Horwich M.D., Hung J.-H., Xu J., Ghildiyal M., Weng Z., et al. Target RNA-directed trimming and tailing of small silencing RNAs. Science 2010, 328:1534-1539. 10.1126/science.1187058.
139. Mullen T.E., Marzluff W.F. Degradation of histone mRNA requires oligouridylation followed by decapping and simultaneous degradation of the mRNA both 5' to 3' and 3' to 5'. Genes Dev. 2008, 22:50-65. 10.1101/gad.1622708.
140. Li J., Yang Z., Yu B., Liu J., Chen X. Methylation protects miRNAs and siRNAs from a 3'-end uridylation activity in Arabidopsis. Curr. Biol. 2005, 15:1501-1507. 10.1016/j.cub.2005.07.029.
141. Chen C., Jin J., James D.A., Adams-Cioaba M.A., Park J.G., Guo Y., et al. Mouse Piwi interactome identifies binding mechanism of Tdrkh Tudor domain to arginine methylated Miwi. Proc. Natl. Acad. Sci. U. S. A. 2009, 106:20336-20341. 10.1073/pnas.0911640106.
142. Kirino Y., Kim N., de Planell-Saguer M., Khandros E., Chiorean S., Klein P.S., et al. Arginine methylation of Piwi proteins catalysed by dPRMT5 is required for Ago3 and Aub stability. Nat. Cell Biol. 2009, 11:652-658. 10.1038/ncb1872.
143. Nishida K.M., Okada T.N., Kawamura T., Mituyama T., Kawamura Y., Inagaki S., et al. Functional involvement of Tudor and dPRMT5 in the piRNA processing pathway in Drosophila germlines. EMBO J. 2009, 28:3820-3831. 10.1038/emboj.2009.365.
144. Huang H.-Y., Houwing S., Kaaij L.J.T., Meppelink A., Redl S., Gauci S., et al. Tdrd1 acts as a molecular scaffold for Piwi proteins and piRNA targets in zebrafish. EMBO J. 2011, 30:3298-3308. 10.1038/emboj.2011.228.
145. Rouhana L., Vieira A.P., Roberts-Galbraith R.H., Newmark P.a. PRMT5 and the role of symmetrical dimethylarginine in chromatoid bodies of planarian stem cells. Development 2012, 139:1083-1094. 10.1242/dev.076182.
146. Reuter M., Chuma S., Tanaka T., Franz T., Stark A., Pillai R.S. 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, 16:639-646. 10.1038/nsmb.1615.
147. Vagin V.V., Wohlschlegel J., Qu J., Jonsson Z., Huang X., Chuma S., et al. Proteomic analysis of murine Piwi proteins reveals a role for arginine methylation in specifying interaction with Tudor family members. Genes Dev. 2009, 23:1749-1762. 10.1101/gad.1814809.
148. Chen C., Nott T.J., Jin J., Pawson T. Deciphering arginine methylation: Tudor tells the tale. Nat. Rev. Mol. Cell Biol. 2011, 12:629-642. 10.1038/nrm3185.
149. Kawaoka S., Arai Y., Kadota K., Suzuki Y., Hara K., Sugano S., et al. Zygotic amplification of secondary piRNAs during silkworm embryogenesis. RNA 2011, 17:1401-1407. 10.1261/rna.2709411.
150. Xiol J., Spinelli P., Laussmann M.A., Homolka D., Yang Z., Cora E., et al. RNA clamping by Vasa assembles a piRNA amplifier complex on transposon transcripts. Cell 2014, 157:1698-1711. 10.1016/j.cell.2014.05.018.
151. Wang W., Yoshikawa M., Han B.W., Izumi N., Tomari Y., Weng Z., et al. The initial uridine of primary piRNAs does not create the tenth adenine that is the hallmark of secondary piRNAs. Mol. Cell 2014, 56:708-716. 10.1016/j.molcel.2014.10.016.
152. Aravin A.A., Sachidanandam R., Girard A., Fejes-Toth K., Hannon G.J. Developmentally regulated piRNA clusters implicate MILI in transposon control. Science 2007, 316:744-747. 10.1126/science.1142612.
153. Kawaoka S., Hayashi N., Suzuki Y., Abe H., Sugano S., Tomari Y., et al. The Bombyx ovary-derived cell line endogenously expresses PIWI/PIWI-interacting RNA complexes. RNA 2009, 15:1258-1264. 10.1261/rna.1452209.
154. Wei Z., Liu X., Zhang H. Identification and characterization of piRNA-like small RNAs in the gonad of sea urchin (Strongylocentrotus nudus). Mar. Biotechnol. (NY) 2012, 14:459-467. 10.1007/s10126-011-9426-z.
155. Palakodeti D., Smielewska M., Lu Y.-C., Yeo G.W., Graveley B.R. The PIWI proteins SMEDWI-2 and SMEDWI-3 are required for stem cell function and piRNA expression in planarians. RNA 2008, 14:1174-1186. 10.1261/rna.1085008.
156. Nishida K.M., Iwasaki Y.W., Murota Y., Nagao A., Mannen T., Kato Y., et al. Respective functions of two distinct siwi complexes assembled during PIWI-interacting RNA biogenesis in Bombyx germ cells. Cell Rep. 2015, 10:193-203. 10.1016/j.celrep.2014.12.013.
157. Gustafson E.A., Wessel G.M. Vasa genes: emerging roles in the germ line and in multipotent cells. Bioessays 2010, 32:626-637. 10.1002/bies.201000001.
158. Khurana J.S., Wang J., Xu J., Koppetsch B.S., Thomson T.C., Nowosielska A., et al. Adaptation to P element transposon invasion in Drosophila melanogaster. Cell 2011, 147:1551-1563. 10.1016/j.cell.2011.11.042.
159. Grentzinger T., Armenise C., Brun C., Mugat B., Serrano V., Pelisson A., et al. piRNA-mediated transgenerational inheritance of an acquired trait. Genome Res. 2012, 22:1877-1888. 10.1101/gr.1366.14.111.
160. Bagijn M.P., Goldstein L.D., Sapetschnig A., Weick E.-M., Bouasker S., Lehrbach N.J., et al. Function, targets, and evolution of Caenorhabditis elegans piRNAs. Science 2012, 337:574-578. 10.1126/science.1220952.
161. Beyret E., Liu N., Lin H. piRNA biogenesis during adult spermatogenesis in mice is independent of the ping-pong mechanism. Cell Res. 2012, 22:1429-1439. 10.1038/cr.2012.120.
162. Lee H.-C., Gu W., Shirayama M., Youngman E., Conte D., Mello C.C. C. elegans piRNAs mediate the genome-wide surveillance of germline transcripts. Cell 2012, 150:78-87. 10.1016/j.cell.2012.06.016.
163. Eyre-Walker A., Keightley P.D. The distribution of fitness effects of new mutations. Nat. Rev. Genet. 2007, 8:610-618. 10.1038/nrg2146.
164. Deragon J.M., Capy P. Impact of transposable elements on the human genome. Ann. Med. 2000, 32:264-273.
165. McDonald J.F. Evolution and consequences of transposable elements. Curr. Opin. Genet. Dev. 1993, 3:855-864.
166. Kalmykova A.I., Klenov M.S., Gvozdev V.A. Argonaute protein PIWI controls mobilization of retrotransposons in the Drosophila male germline. Nucleic Acids Res. 2005, 33:2052-2059. 10.1093/nar/gki323.
167. Vagin V.V., Klenov M.S., Kalmykova A.I., Stolyarenko A.D., Kotelnikov R.N., Gvozdev V.A. The RNA interference proteins and vasa locus are involved in the silencing of retrotransposons in the female germline of Drosophila melanogaster. RNA Biol. 2004, 1:54-58.
168. Czech B., Malone C.D., Zhou R., Stark A., Schlingeheyde C., Dus M., et al. An endogenous small interfering RNA pathway in Drosophila. Nature 2008, 453:798-802. 10.1038/nature07007.
169. Sijen T., Plasterk R.H.A. Transposon silencing in the Caenorhabditis elegans germ line by natural RNAi. Nature 2003, 426:310-314. 10.1038/nature02107.
170. Nagao A., Mituyama T., Huang H., Chen D., Siomi M.C., Siomi H. Biogenesis pathways of piRNAs loaded onto AGO3 in the Drosophila testis. RNA 2010, 16:2503-2515. 10.1261/rna.2270710.
171. Mani S.R., Juliano C.E. Untangling the web: the diverse functions of the PIWI/piRNA pathway. Mol. Reprod. Dev. 2013, 80:632-664. 10.1002/mrd.22195.
172. Kuramochi-Miyagawa S., Watanabe T., Gotoh K., Totoki Y., Toyoda A., Ikawa M., et al. DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes. Genes Dev. 2008, 22:908-917.
173. Huang X.a., Yin H., Sweeney S., Raha D., Snyder M., Lin H. A major epigenetic programming mechanism guided by piRNAs. Dev. Cell 2013, 24:502-516. 10.1016/j.devcel.2013.01.023.
174. Klenov M.S., Lavrov S.A., Korbut A.P., Stolyarenko A.D., Yakushev E.Y., Reuter M., et al. Impact of nuclear Piwi elimination on chromatin state in Drosophila melanogaster ovaries. Nucleic Acids Res. 2014, 42:6208-6218. 10.1093/nar/gku268.
175. Le Thomas A., Rogers A.K., Webster A., Marinov G.K., Liao S.E., Perkins E.M., et al. Piwi induces piRNA-guided transcriptional silencing and establishment of a repressive chromatin state. Genes Dev. 2013, 27:390-399. 10.1101/gad.209841.112.
176. Rozhkov N.V., Hammell M., Hannon G.J. Multiple roles for Piwi in silencing Drosophila transposons. Genes Dev. 2013, 27:400-412. 10.1101/gad.209767.112.
177. Sienski G., Dönertas D., Brennecke J. Transcriptional silencing of transposons by Piwi and maelstrom and its impact on chromatin state and gene expression. Cell 2012, 151:964-980. 10.1016/j.cell.2012.10.040.
178. Wang S.H., Elgin S.C.R. Drosophila Piwi functions downstream of piRNA production mediating a chromatin-based transposon silencing mechanism in female germ line. Proc. Natl. Acad. Sci. U.S.A. 2011, 108:21164-21169. 10.1073/pnas.1107892109.
179. Pal-Bhadra M., Leibovitch B.A., Gandhi S.G., Chikka M.R., Rao M., Bhadra U., et al. Heterochromatic silencing and HP1 localization in Drosophila are dependent on the RNAi machinery. Science 2004, 303:669-672. 10.1126/science.1092653.
180. De Fazio S., Bartonicek N., Di Giacomo M., Abreu-Goodger C., Sankar A., Funaya C., et al. The endonuclease activity of Mili fuels piRNA amplification that silences LINE1 elements. Nature 2011, 480:259-263. 10.1038/nature10547.
181. Darricarrère N., Liu N., Watanabe T., Lin H. Function of Piwi, a nuclear Piwi/Argonaute protein, is independent of its slicer activity. Proc. Natl. Acad. Sci. U. S. A. 2013, 110:1297-1302. 10.1073/pnas.1213283110.
182. Yin H., Lin H. An epigenetic activation role of Piwi and a Piwi-associated piRNA in Drosophila melanogaster. Nature 2007, 450:304-308. 10.1038/nature06263.
183. Dönertas D., Sienski G., Brennecke J. Drosophila Gtsf1 is an essential component of the Piwi-mediated transcriptional silencing complex. Genes Dev. 2013, 27:1693-1705. 10.1101/gad.221150.113.
184. Muerdter F., Guzzardo P.M., Gillis J., Luo Y., Yu Y., Chen C., et al. A genome-wide RNAi screen draws a genetic framework for transposon control and primary piRNA biogenesis in Drosophila. Mol. Cell 2013, 50:736-748. 10.1016/j.molcel.2013.04.006.
185. Nishida K.M., Saito K., Mori T., Kawamura Y., Nagami-Okada T., Inagaki S., et al. Gene silencing mechanisms mediated by Aubergine piRNA complexes in Drosophila male gonad. RNA 2007, 13:1911-1922. 10.1261/rna.744307.
186. Tatsuke T., Sakashita K., Masaki Y., Lee J.M., Kawaguchi Y., Kusakabe T. The telomere-specific non-LTR retrotransposons SART1 and TRAS1 are suppressed by Piwi subfamily proteins in the silkworm, Bombyx mori. Cell. Mol. Biol. Lett. 2010, 15:118-133. 10.2478/s11658-009-0038-9.
187. Mani S.R., Megosh H., Lin H. PIWI proteins are essential for early Drosophila embryogenesis. Dev. Biol. 2014, 385:340-349. 10.1016/j.ydbio.2013.10.017.
188. Megosh H.B., Cox D.N., Campbell C., Lin H. The role of PIWI and the miRNA machinery in Drosophila germline determination. Curr. Biol. 2006, 16:1884-1894. 10.1016/j.cub.2006.08.051.
189. Gou L.-T., Dai P., Yang J.-H., Xue Y., Hu Y.-P., Zhou Y., et al. Pachytene piRNAs instruct massive mRNA elimination during late spermiogenesis. Cell Res. 2014, 24:680-700. 10.1038/cr.2014.41.
190. Watanabe T., Cheng E.-C., Zhong M., Lin H. Retrotransposons and pseudogenes regulate mRNAs and lncRNAs via the piRNA pathway in the germline. Genome Res. 2015, 25:368-380. 10.1101/gr.180802.114.
191. Cox D.N., Chao A., Baker J., Chang L., Qiao D., Lin H. A novel class of evolutionarily conserved genes defined by piwi are essential for stem cell self-renewal. Genes Dev. 1998, 12:3715-3727. 10.1101/gad.12.23.3715.
192. Cox D.N., Chao A., Lin H. piwi encodes a nucleoplasmic factor whose activity modulates the number and division rate of germline stem cells. Development 2000, 127:503-514.
193. Szakmary A., Cox D.N., Wang Z., Lin H. Regulatory relationship among piwi, pumilio, and bag-of-marbles in Drosophila germline stem cell self-renewal and differentiation. Curr. Biol. 2005, 15:171-178. 10.1016/j.cub.2005.01.005.
194. Klenov M.S., Sokolova O.A., Yakushev E.Y., Stolyarenko A.D., Mikhaleva E.A., Lavrov S.A., et al. Separation of stem cell maintenance and transposon silencing functions of Piwi protein. Proc. Natl. Acad. Sci. U. S. A. 2011, 108:18760-18765. 10.1073/pnas.1106676108.
195. Jin Z., Flynt A.S., Lai E.C. Drosophila piwi mutants exhibit germline stem cell tumors that are sustained by elevated Dpp signaling. Curr. Biol. 2013, 23:1442-1448. 10.1016/j.cub.2013.06.021.
196. Ma X., Wang S., Do T., Song X., Inaba M., Nishimoto Y., et al. Piwi is required in multiple cell types to control germline stem cell lineage development in the Drosophila ovary. PLoS ONE 2014, 9:e90267. 10.1371/journal.pone.0090267.
197. Pek J.W., Kai T. A role for vasa in regulating mitotic chromosome condensation in Drosophila. Curr. Biol. 2011, 21:39-44. 10.1016/j.cub.2010.11.051.
198. Unhavaithaya Y., Hao Y., Beyret E., Yin H., Kuramochi-Miyagawa S., Nakano T., et al. 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. 2009, 284:6507-6519. 10.1074/jbc.M809104200.
199. Zhao S., Gou L.-T., Zhang M., Zu L.-D., Hua M.-M., Hua Y., et al. piRNA-triggered MIWI ubiquitination and removal by APC/C in late spermatogenesis. Dev. Cell 2013, 24:13-25. 10.1016/j.devcel.2012.12.006.
200. Ewen-Campen B., Donoughe S., Clarke D.N., Extavour C.G. Germ cell specification requires zygotic mechanisms rather than germ plasm in a basally branching insect. Curr. Biol. 2013, 23:835-842. 10.1016/j.cub.2013.03.063.
201. Brennecke J., Malone C.D., Aravin A.A., Sachidanandam R., Stark A., Hannon G.J. An epigenetic role for maternally inherited piRNAs in transposon silencing. Science 2008, 322:1387-1392. 10.1126/science.1165171.
202. Chambeyron S., Popkova A., Payen-Groschêne G., Brun C., Laouini D., Pelisson A., et al. piRNA-mediated nuclear accumulation of retrotransposon transcripts in the Drosophila female germline. Proc. Natl. Acad. Sci. U. S. A. 2008, 105:14964-14969. 10.1073/pnas.0805943105.
203. Rubin G.M., Kidwell M.G., Bingham P.M. The molecular basis of P-M hybrid dysgenesis: the nature of induced mutations. Cell 1982, 29:987-994.
204. Pélisson A. The I-R system of hybrid dysgenesis in Drosophila melanogaster: are I factor insertions responsible for the mutator effect of the I-R interaction?. Mol. Gen. Genet. 1981, 183:123-129.
205. Bucheton A., Paro R., Sang H.M., Pelisson A., Finnegan D.J. The molecular basis of I-R hybrid dysgenesis in Drosophila melanogaster: identification, cloning, and properties of the I factor. Cell 1984, 38:153-163.
206. Kidwell M.G. Evolution of hybrid dysgenesis determinants in Drosophila melanogaster. Proc. Natl. Acad. Sci. U. S. A. 1983, 80:1655-1659.
207. Castro J.P., Carareto C.M.A. Drosophila melanogaster P transposable elements: mechanisms of transposition and regulation. Genetica 2004, 121:107-118.
208. Chambeyron S., Bucheton A. I elements in Drosophila: in vivo retrotransposition and regulation. Cytogenet. Genome Res. 2005, 110:215-222. 10.1159/000084955.
209. De Vanssay A., Bougé A.-L., Boivin A., Hermant C., Teysset L., Delmarre V., et al. Paramutation in Drosophila linked to emergence of a piRNA-producing locus. Nature 2012, 490:112-115. 10.1038/nature11416.
210. Brink R.A. A genetic change associated with the R locus in maize which is directed and potentially reversible. Genetics 1956, 41:872-889.
211. Coe E.H. A regular and continuing conversion type phenomenon at the B locus in maize. Proc. Natl. Acad. Sci. U. S. A. 1959, 45:828-832.
212. Josse T., Teysset L., Todeschini A.-L., Sidor C.M., Anxolabéhère D., Ronsseray S. Telomeric trans-silencing: an epigenetic repression combining RNA silencing and heterochromatin formation. PLoS Genet. 2007, 3:1633-1643. 10.1371/journal.pgen.0030158.
213. Todeschini A.-L., Teysset L., Delmarre V., Ronsseray S. The epigenetic trans-silencing effect in Drosophila involves maternally-transmitted small RNAs whose production depends on the piRNA pathway and HP1. PLoS ONE 2010, 5:e11032. 10.1371/journal.pone.0011032.
214. Ashe A., Sapetschnig A., Weick E.-M., Mitchell J., Bagijn M.P., Cording A.C., et al. piRNAs can trigger a multigenerational epigenetic memory in the germline of C. elegans. Cell 2012, 150:88-99. 10.1016/j.cell.2012.06.018.
215. Shirayama M., Seth M., Lee H.-C., Gu W., Ishidate T., Conte D., et al. piRNAs initiate an epigenetic memory of nonself RNA in the C. elegans germline. Cell 2012, 150:65-77. 10.1016/j.cell.2012.06.015.
216. Luteijn M.J., van Bergeijk P., Kaaij L.J.T., Almeida M.V., Roovers E.F., Berezikov E., et al. Extremely stable Piwi-induced gene silencing in Caenorhabditis elegans. EMBO J. 2012, 31:3422-3430. 10.1038/emboj.2012.213.
217. Buckley B.A., Burkhart K.B., Gu S.G., Spracklin G., Kershner A., Fritz H., et al. A nuclear Argonaute promotes multigenerational epigenetic inheritance and germline immortality. Nature 2012, 489:447-451. 10.1038/nature11352.
218. Ross R.J., Weiner M.M., Lin H. PIWI proteins and PIWI-interacting RNAs in the soma. Nature 2014, 505:353-359. 10.1038/nature12987.
219. Khurana J.S., Xu J., Weng Z., Theurkauf W.E. Distinct functions for the Drosophila piRNA pathway in genome maintenance and telomere protection. PLoS Genet. 2010, 6:e1001246. 10.1371/journal.pgen.1001246.
220. Schwager E.E., Meng Y., Extavour C.G. vasa and piwi are required for mitotic integrity in early embryogenesis in the spider Parasteatoda tepidariorum. Dev. Biol. 2014, 10.1016/j.ydbio.2014.08.032.
221. Gu T., Elgin S.C.R. Maternal depletion of Piwi, a component of the RNAi system, impacts heterochromatin formation in Drosophila. PLoS Genet. 2013, 9:e1003780. 10.1371/journal.pgen.1003780.
222. Akkouche A., Grentzinger T., Fablet M., Armenise C., Burlet N., Braman V., et al. Maternally deposited germline piRNAs silence the tirant retrotransposon in somatic cells. EMBO Rep. 2013, 14:458-464. 10.1038/embor.2013.38.
223. Rodriguez A.J., Seipel S.A., Hamill D.R., Romancino D.P., Di carlo M., Suprenant K.A., et al. Seawi-a sea urchin piwi/argonaute family member is a component of MT-RNP complexes. RNA 2005, 11:646-656. 10.1261/rna.7198205.
224. Grivna S.T., Pyhtila B., Lin H. MIWI associates with translational machinery and PIWI-interacting RNAs (piRNAs) in regulating spermatogenesis. Proc. Natl. Acad. Sci. U. S. A. 2006, 103:13415-13420. 10.1073/pnas.0605506103.
225. Wilson J.E., Connell J.E., Macdonald P.M. Aubergine enhances oskar translation in the Drosophila ovary. Development 1996, 122:1631-1639.
226. Rouget C., Papin C., Boureux A., Meunier A.-C., Franco B., Robine N., et al. Maternal mRNA deadenylation and decay by the piRNA pathway in the early Drosophila embryo. Nature 2010, 467:1128-1132. 10.1038/nature09465.
227. Kawaoka S., Kadota K., Arai Y., Suzuki Y., Fujii T., Abe H., et al. The silkworm W chromosome is a source of female-enriched piRNAs. RNA 2011, 17:2144-2151. 10.1261/rna.027565.111.
228. Kiuchi T., Koga H., Kawamoto M., Shoji K., Sakai H., Arai Y., et al. A single female-specific piRNA is the primary determiner of sex in the silkworm. Nature 2014, 509:633-636. 10.1038/nature13315.
229. Gangaraju V.K., Yin H., Weiner M.M., Wang J., Huang X.A., Lin H. Drosophila Piwi functions in Hsp90-mediated suppression of phenotypic variation. Nat. Genet. 2011, 43:153-158. 10.1038/ng.743.
230. Specchia V., Piacentini L., Tritto P., Fanti L., D'Alessandro R., Palumbo G., et al. Hsp90 prevents phenotypic variation by suppressing the mutagenic activity of transposons. Nature 2010, 463:662-665. 10.1038/nature08739.
231. Waddington C.H. Canalization of development and the inheritance of acquired characters. Nature 1942, 150:563-565. 10.1038/150563a0.
232. Rajasethupathy P., Antonov I., Sheridan R., Frey S., Sander C., Tuschl T., et al. A role for neuronal piRNAs in the epigenetic control of memory-related synaptic plasticity. Cell 2012, 149:693-707. 10.1016/j.cell.2012.02.057.
233. Lee E.J., Banerjee S., Zhou H., Jammalamadaka A., Arcila M., Manjunath B.S., et al. Identification of piRNAs in the central nervous system. RNA 2011, 17:1090-1099. 10.1261/rna.2565011.
234. Perrat P.N., DasGupta S., Wang J., Theurkauf W., Weng Z., Rosbash M., et al. Transposition-driven genomic heterogeneity in the Drosophila brain. Science 2013, 340:91-95. 10.1126/science.1231965.
235. Muotri A.R., Chu V.T., Marchetto M.C.N., Deng W., Moran J.V., Gage F.H. Somatic mosaicism in neuronal precursor cells mediated by L1 retrotransposition. Nature 2005, 435:903-910. 10.1038/nature03663.
236. Muotri A.R., Zhao C., Marchetto M.C.N., Gage F.H. Environmental influence on L1 retrotransposons in the adult hippocampus. Hippocampus 2009, 19:1002-1007. 10.1002/hipo.20564.
237. Coufal N.G., Garcia-Perez J.L., Peng G.E., Yeo G.W., Mu Y., Lovci M.T., et al. L1 retrotransposition in human neural progenitor cells. Nature 2009, 460:1127-1131. 10.1038/nature08248.
238. Baillie J.K., Barnett M.W., Upton K.R., Gerhardt D.J., Richmond T.A., De Sapio F., et al. Somatic retrotransposition alters the genetic landscape of the human brain. Nature 2011, 479:534-537. 10.1038/nature10531.
239. Alié A., Leclère L., Jager M., Dayraud C., Chang P., Le Guyader H., et al. Somatic stem cells express Piwi and Vasa genes in an adult ctenophore: ancient association of "germline genes" with stemness. Dev. Biol. 2011, 350:183-197. 10.1016/j.ydbio.2010.10.019.
240. Denker E., Manuel M., Leclère L., Le Guyader H., Rabet N. Ordered progression of nematogenesis from stem cells through differentiation stages in the tentacle bulb of Clytia hemisphaerica (Hydrozoa, Cnidaria). Dev. Biol. 2008, 315:99-113. 10.1016/j.ydbio.2007.12.023.
241. Funayama N., Nakatsukasa M., Mohri K., Masuda Y., Agata K. Piwi expression in archeocytes and choanocytes in demosponges: insights into the stem cell system in demosponges. Evol. Dev. 2010, 12:275-287. 10.1111/j.1525-142X.2010.00413.x.
242. Mochizuki K., Sano H., Kobayashi S., Nishimiya-Fujisawa C., Fujisawa T. Expression and evolutionary conservation of nanos-related genes in Hydra. Dev. Genes Evol. 2000, 210:591-602.
243. Mochizuki K., Nishimiya-Fujisawa C., Fujisawa T. Universal occurrence of the vasa-related genes among metazoans and their germline expression in Hydra. Dev. Genes Evol. 2001, 211:299-308.
244. Seipel K., Yanze N., Schmid V. The germ line and somatic stem cell gene Cniwi in the jellyfish Podocoryne carnea. Int. J. Dev. Biol. 2004, 48:1-7.
245. Juliano C., Wessel G. Versatile germline genes. Science 2010, 329:640-641. 10.1126/science.1194037.
246. Juliano C.E., Swartz S.Z., Wessel G.M. A conserved germline multipotency program. Development 2010, 137:4113-4126. 10.1242/dev.047969.
247. Hobmayer B., Jenewein M., Eder D., Eder M.-K., Glasauer S., Gufler S., et al. Stemness in Hydra-a current perspective. Int. J. Dev. Biol. 2012, 56:509-517. 10.1387/ijdb.113426bh.
248. Holstein T.W., Hess M.W., Salvenmoser W. Preparation techniques for transmission electron microscopy of Hydra. Methods Cell Biol. 2010, 96:285-306. 10.1016/S0091-679X(10)96013-5.
249. Noda K., Kanai C. An ultrastructural observation of Pelmatohydra robusta at sexual and asexual stages, with a special reference to "germinal plasm". J. Ultrastruct. Res. 1977, 61:284-294.
250. Coward S.J. Chromatoid bodies in somatic cells of the planarian: observations on their behavior during mitosis. Anat. Rec. 1974, 180:533-545. 10.1002/ar.1091800312.
251. Hay E.D., Coward S.J. Fine structure studies on the planarian, Dugesia. I. Nature of the "neoblast" and other cell types in noninjured worms. J. Ultrastruct. Res. 1975, 50:1-21.
252. Morita M., Best J.B., Noel J. Electron microscopic studies of planarian regeneration. I. Fine structure of neoblasts in Dugesia dorotocephala. J. Ultrastruct. Res. 1969, 27:7-23.
253. Hori I. An ultrastructural study of the chromatoid body in planarian regenerative cells. Microscope 1982, 31:63-72.
254. Pfister D., De Mulder K., Hartenstein V., Kuales G., Borgonie G., Marx F., et al. Flatworm stem cells and the germ line: developmental and evolutionary implications of macvasa expression in Macrostomum lignano. Dev. Biol. 2008, 319:146-159. 10.1016/j.ydbio.2008.02.045.
255. De Sutter D., Van de Vyver G. Isolation and recognition properties of some definite sponge cell types. Dev. Comp. Immunol. 1979, 3:389-397.
256. Buscema M., Sutter D., Van de Vyver G. Ultrastructural study of differentiation processes during aggregation of purified sponge archaeocytes. Wilhelm Roux's Arch. Dev. Biol. 1980, 188:45-53. 10.1007/BF00848609.
257. Plickert G., Frank U., Müller W.A. Hydractinia, a pioneering model for stem cell biology and reprogramming somatic cells to pluripotency. Int. J. Dev. Biol. 2012, 56:519-534. 10.1387/ijdb.123502gp.
258. Reddien P.W., Oviedo N.J., Jennings J.R., Jenkin J.C., Sánchez Alvarado A. SMEDWI-2 is a PIWI-like protein that regulates planarian stem cells. Science 2005, 310:1327-1330. 10.1126/science.1116110.
259. Rossi L., Salvetti A., Lena A., Batistoni R., Deri P., Pugliesi C., et al. DjPiwi-1, a member of the PAZ-Piwi gene family, defines a subpopulation of planarian stem cells. Dev. Genes Evol. 2006, 216:335-346. 10.1007/s00427-006-0060-0.
260. Guo T., Peters A.H.F.M., Newmark P.A. A Bruno-like gene is required for stem cell maintenance in planarians. Dev. Cell 2006, 11:159-169. 10.1016/j.devcel.2006.06.004.
261. Zeng A., Li Y.-Q., Wang C., Han X.-S., Li G., Wang J.-Y., et al. Heterochromatin protein 1 promotes self-renewal and triggers regenerative proliferation in adult stem cells. J. Cell Biol. 2013, 201:409-425. 10.1083/jcb.201207172.
262. Wagner D.E., Ho J.J., Reddien P.W. Genetic regulators of a pluripotent adult stem cell system in planarians identified by RNAi and clonal analysis. Cell Stem Cell 2012, 10:299-311. 10.1016/j.stem.2012.01.016.
263. De Mulder K., Kuales G., Pfister D., Willems M., Egger B., Salvenmoser W., et al. Characterization of the stem cell system of the acoel Isodiametra pulchra. BMC Dev. Biol. 2009, 9:69. 10.1186/1471-213X-9-69.
264. Srivastava M., Mazza-Curll K.L., van Wolfswinkel J.C., Reddien P.W. Whole-body acoel regeneration is controlled by Wnt and Bmp-Admp signaling. Curr. Biol. 2014, 24:1107-1113. 10.1016/j.cub.2014.03.042.
265. De Rosa R., Prud'homme B., Balavoine G. Caudal and even-skipped in the annelid Platynereis dumerilii and the ancestry of posterior growth. Evol. Dev. 2005, 7:574-587. 10.1111/j.1525-142X.2005.05061.x.
266. Janssen R., Le Gouar M., Pechmann M., Poulin F., Bolognesi R., Schwager E.E., et al. Conservation, loss, and redeployment of Wnt ligands in protostomes: implications for understanding the evolution of segment formation. BMC Evol. Biol. 2010, 10:374. 10.1186/1471-2148-10-374.
267. Rebscher N., Zelada-González F., Banisch T.U., Raible F., Arendt D. Vasa unveils a common origin of germ cells and of somatic stem cells from the posterior growth zone in the polychaete Platynereis dumerilii. Dev. Biol. 2007, 306:599-611. 10.1016/j.ydbio.2007.03.521.
268. Gazave E., Béhague J., Laplane L., Guillou A., Préau L., Demilly A., et al. Posterior elongation in the annelid Platynereis dumerilii involves stem cells molecularly related to primordial germ cells. Dev. Biol. 2013, 382:246-267. 10.1016/j.ydbio.2013.07.013.
269. Giani V.C., Yamaguchi E., Boyle M.J., Seaver E.C. Somatic and germline expression of piwi during development and regeneration in the marine polychaete annelid Capitella teleta. Evodevo 2011, 2:10. 10.1186/2041-9139-2-10.
270. Zhang Q.-J., Luo Y.-J., Wu H.-R., Chen Y.-T., Yu J.-K. Expression of germline markers in three species of amphioxus supports a preformation mechanism of germ cell development in cephalochordates. Evodevo 2013, 4:17. 10.1186/2041-9139-4-17.
271. Rosner A., Moiseeva E., Rinkevich Y., Lapidot Z., Rinkevich B. Vasa and the germ line lineage in a colonial urochordate. Dev. Biol. 2009, 331:113-128. 10.1016/j.ydbio.2009.04.025.
272. Rinkevich Y., Voskoboynik A., Rosner A., Rabinowitz C., Paz G., Oren M., et al. Repeated, long-term cycling of putative stem cells between niches in a basal chordate. Dev. Cell 2013, 24:76-88. 10.1016/j.devcel.2012.11.010.
273. Rinkevich Y., Rosner A., Rabinowitz C., Lapidot Z., Moiseeva E., Rinkevich B. Piwi positive cells that line the vasculature epithelium, underlie whole body regeneration in a basal chordate. Dev. Biol. 2010, 345:94-104. 10.1016/j.ydbio.2010.05.500.
274. Wu Q., Ma Q., Shehadeh L.A., Wilson A., Xia L., Yu H., et al. Expression of the Argonaute protein PiwiL2 and piRNAs in adult mouse mesenchymal stem cells. Biochem. Biophys. Res. Commun. 2010, 396:915-920. 10.1016/j.bbrc.2010.05.022.
275. Sharma A.K., Nelson M.C., Brandt J.E., Wessman M., Mahmud N., Weller K.P., et al. Human CD34(+) stem cells express the hiwi gene, a human homologue of the Drosophila gene piwi. Blood 2001, 97:426-434.
276. Nolde M.J., Cheng E.-C., Guo S., Lin H. Piwi genes are dispensable for normal hematopoiesis in mice. PLoS ONE 2013, 8:e71950. 10.1371/journal.pone.0071950.
277. Chen L., Shen R., Ye Y., Pu X.-A., Liu X., Duan W., et al. Precancerous stem cells have the potential for both benign and malignant differentiation. PLoS ONE 2007, 2:e293. 10.1371/journal.pone.0000293.
278. Tanaka E.M., Reddien P.W. The cellular basis for animal regeneration. Dev. Cell 2011, 21:172-185. 10.1016/j.devcel.2011.06.016.
279. Zhu W., Pao G.M., Satoh A., Cummings G., Monaghan J.R., Harkins T.T., et al. Activation of germline-specific genes is required for limb regeneration in the Mexican axolotl. Dev. Biol. 2012, 370:42-51. 10.1016/j.ydbio.2012.07.021.
280. Mikkelsen T.S., Hanna J., Zhang X., Ku M., Wernig M., Schorderet P., et al. Dissecting direct reprogramming through integrative genomic analysis. Nature 2008, 454:49-55. 10.1038/nature07056.
281. Marchetto M.C.N., Narvaiza I., Denli A.M., Benner C., Lazzarini T.A., Nathanson J.L., et al. Differential L1 regulation in pluripotent stem cells of humans and apes. Nature 2013, 503:525-529. 10.1038/nature12686.
282. Cheng E.-C., Kang D., Wang Z., Lin H. PIWI proteins are dispensable for mouse somatic development and reprogramming of fibroblasts into pluripotent stem cells. PLoS ONE 2014, 9:e97821. 10.1371/journal.pone.0097821.
283. Qiao D., Zeeman A.-M., Deng W., Looijenga L.H.J., Lin H. Molecular characterization of hiwi, a human member of the piwi gene family whose overexpression is correlated to seminomas. Oncogene 2002, 21:3988-3999. 10.1038/sj.onc.1205505.
284. Liu X., Sun Y., Guo J., Ma H., Li J., Dong B., et al. Expression of hiwi gene in human gastric cancer was associated with proliferation of cancer cells. Int. J. Cancer 2006, 118:1922-1929. 10.1002/ijc.21575.
285. Grochola L.F., Greither T., Taubert H., Möller P., Knippschild U., Udelnow A., et al. The stem cell-associated Hiwi gene in human adenocarcinoma of the pancreas: expression and risk of tumour-related death. Br. J. Cancer 2008, 99:1083-1088. 10.1038/sj.bjc.6604653.
286. Lee J.H., Schütte D., Wulf G., Füzesi L., Radzun H.-J., Schweyer S., et al. Stem-cell protein Piwil2 is widely expressed in tumors and inhibits apoptosis through activation of Stat3/Bcl-XL pathway. Hum. Mol. Genet. 2006, 15:201-211. 10.1093/hmg/ddi430.
287. Lee J.H., Jung C., Javadian-Elyaderani P., Schweyer S., Schütte D., Shoukier M., et al. Pathways of proliferation and antiapoptosis driven in breast cancer stem cells by stem cell protein piwil2. Cancer Res. 2010, 70:4569-4579. 10.1158/0008-5472.CAN-09-2670.
288. Wang Y., Liu Y., Shen X., Zhang X., Chen X., Yang C., et al. The PIWI protein acts as a predictive marker for human gastric cancer. Int. J. Clin. Exp. Pathol. 2012, 5:315-325.
289. Liang D., Yang Y., Liu Y. The role Hiwi gene in the maintenance of lung cancer stem cell populations. Neoplasma 2013, 10.4149/neo_2014_022.
290. Zhao Y.-M., Zhou J.-M., Wang L.-R., He H.-W., Wang X.-L., Tao Z.-H., et al. HIWI is associated with prognosis in patients with hepatocellular carcinoma after curative resection. Cancer 2012, 118:2708-2717. 10.1002/cncr.26524.
291. Chen Y., Hu W., Lu Y., Jiang S., Li C., Chen J., et al. A TALEN-based specific transcript knock-down of PIWIL2 suppresses cell growth in HepG2 tumor cell. Cell Prolif. 2014, 47:448-456. 10.1111/cpr.12120.
292. Wang X., Tong X., Gao H., Yan X., Xu X., Sun S., et al. Silencing HIWI suppresses the growth, invasion and migration of glioma cells. Int. J. Oncol. 2014, 45:2385-2392.
293. Xie Y., Yang Y., Ji D., Zhang D., Yao X., Zhang X. Hiwi downregulation, mediated by shRNA, reduces the proliferation and migration of human hepatocellular carcinoma cells. Mol. Med. Rep. 2014, 10.3892/mmr.2014.2847.
294. Yao Y., Li C., Zhou X., Zhang Y., Lu Y., Chen J., et al. PIWIL2 induces c-Myc expression by interacting with NME2 and regulates c-Myc-mediated tumor cell proliferation. Oncotarget 2014.
295. Chu H., Hui G., Yuan L., Shi D., Wang Y., Du M., et al. Identification of novel piRNAs in bladder cancer. Cancer Lett. 2015, 356:561-567. 10.1016/j.canlet.2014.10.004.
296. Hashim A., Rizzo F., Marchese G., Ravo M., Tarallo R., Nassa G., et al. RNA sequencing identifies specific PIWI-interacting small non-coding RNA expression patterns in breast cancer. Oncotarget 2014, 5:9901-9910.
297. Yan H., Wu Q.-L., Sun C.-Y., Ai L.-S., Deng J., Zhang L., et al. piRNA-823 contributes to tumorigenesis by regulating de novo DNA methylation and angiogenesis in multiple myeloma. Leukemia 2015, 29:196-206. 10.1038/leu.2014.135.
298. Cheng J., Deng H., Xiao B., Zhou H., Zhou F., Shen Z., et al. piR-823, a novel non-coding small RNA, demonstrates in vitro and in vivo tumor suppressive activity in human gastric cancer cells. Cancer Lett. 2012, 315:12-17. 10.1016/j.canlet.2011.10.004.
299. Sun G., Wang Y., Sun L., Luo H., Liu N., Fu Z., et al. Clinical significance of Hiwi gene expression in gliomas. Brain Res. 2011, 1373:183-188. 10.1016/j.brainres.2010.11.097.
300. Taubert H., Greither T., Kaushal D., Würl P., Bache M., Bartel F., et al. Expression of the stem cell self-renewal gene Hiwi and risk of tumour-related death in patients with soft-tissue sarcoma. Oncogene 2007, 26:1098-1100. 10.1038/sj.onc.1209880.
301. Greither T., Koser F., Kappler M., Bache M., Lautenschläger C., Göbel S., et al. Expression of human Piwi-like genes is associated with prognosis for soft tissue sarcoma patients. BMC Cancer 2012, 12:272. 10.1186/1471-2407-12-272.
302. Lim S.L., Ricciardelli C., Oehler M.K., De Arao Tan I.M.D., Russell D., Grützner F. Overexpression of piRNA pathway genes in epithelial ovarian cancer. PLoS ONE 2014, 9:e99687. 10.1371/journal.pone.0099687.
303. Janic A., Mendizabal L., Llamazares S., Rossell D., Gonzalez C. Ectopic expression of germline genes drives malignant brain tumor growth in Drosophila. Science 2010, 330:1824-1827. 10.1126/science.1195481.
304. Millane R.C., Kanska J., Duffy D.J., Seoighe C., Cunningham S., Plickert G., et al. Induced stem cell neoplasia in a cnidarian by ectopic expression of a POU domain transcription factor. Development 2011, 138:2429-2439. 10.1242/dev.064931.
305. Czech B., Preall J.B., McGinn J., Hannon G.J. A transcriptome-wide RNAi screen in the Drosophila ovary reveals factors of the germline piRNA pathway. Mol. Cell 2013, 50:749-761. 10.1016/j.molcel.2013.04.007.
306. Handler D., Meixner K., Pizka M., Lauss K., Schmied C., Gruber F.S., et al. The genetic makeup of the Drosophila piRNA pathway. Mol. Cell 2013, 50:762-777. 10.1016/j.molcel.2013.04.031.
307. Cichocki F., Lenvik T., Sharma N., Yun G., Anderson S.K., Miller J.S. Cutting edge: KIR antisense transcripts are processed into a 28-base PIWI-like RNA in human NK cells. J. Immunol. 2010, 185:2009-2012. 10.4049/jimmunol.1000855.
308. Yan Z., Hu H.Y., Jiang X., Maierhofer V., Neb E., He L., et al. Widespread expression of piRNA-like molecules in somatic tissues. Nucleic Acids Res. 2011, 39:6596-6607. 10.1093/nar/gkr298.