title: One Loop to Rule Them All: The Ping-Pong Cycle and piRNA-Guided Silencing.
abstract: The PIWI-interacting RNA (piRNA) pathway is a conserved defense mechanism that protects the genetic information of animal germ cells from the deleterious effects of molecular parasites, such as transposons. Discovered nearly a decade ago, this small RNA silencing system comprises PIWI-clade Argonaute proteins and their associated RNA-binding partners, the piRNAs. In this review, we highlight recent work that has advanced our understanding of how piRNAs preserve genome integrity across generations. We discuss the mechanism of piRNA biogenesis, give an overview of common themes as well as differences in piRNA-mediated silencing between species, and end by highlighting known and emerging functions of piRNAs.
authors.affiliation: Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge, CB2 0RE, UK. Electronic address: benjamin.czech@cruk.cam.ac.uk.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Czech
authors.affiliation: Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge, CB2 0RE, UK. Electronic address: greg.hannon@cruk.cam.ac.uk.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Hannon
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000235:genetics* / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D020868:Gene Silencing; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D060565:Argonaute Proteins; D002868:Chromosomal Proteins, Non-Histone; C000590395:Cuff protein, Drosophila; D029721:Drosophila Proteins; D006657:Histones; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C583035:del protein, Drosophila; C449641:rhi protein, Drosophila
keywords: PIWI proteins; piRNA biogenesis; ping-pong amplification loop; post-transcriptional gene silencing (PTGS); transcriptional gene silencing (TGS); transposon control
references.citation: RNA. 2014 Dec;20(12):1977-86
references.pmid: 25336588
references.citation: Nature. 2010 Oct 28;467(7319):1128-32
references.pmid: 20953170
references.citation: Science. 2006 Jul 21;313(5785):363-7
references.pmid: 16778019
references.citation: Cell. 2007 Apr 6;129(1):69-82
references.pmid: 17418787
references.citation: Curr Biol. 2011 Nov 22;21(22):1888-93
references.pmid: 22055292
references.citation: Genes Dev. 2008 Apr 1;22(7):908-17
references.pmid: 18381894
references.citation: Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6714-9
references.pmid: 17428915
references.citation: Cell Rep. 2015 Jul 21;12(3):418-28
references.pmid: 26166577
references.citation: Genome Res. 2009 Oct;19(10):1776-85
references.pmid: 19541914
references.citation: EMBO J. 2015 Dec 14;34(24):3009-27
references.pmid: 26471728
references.citation: PLoS Genet. 2009 Sep;5(9):e1000644
references.pmid: 19750210
references.citation: PLoS Genet. 2009 Sep;5(9):e1000635
references.pmid: 19730684
references.citation: Genes Dev. 2015 May 15;29(10):1032-44
references.pmid: 25995188
references.citation: Science. 2015 Oct 16;350(6258):339-42
references.pmid: 26472911
references.citation: Nat Struct Mol Biol. 2013 Mar;20(3):332-8
references.pmid: 23353788
references.citation: Cell. 2014 Jun 5;157(6):1364-1379
references.pmid: 24906153
references.citation: Genes Dev. 2013 Aug 1;27(15):1656-61
references.pmid: 23913921
references.citation: Nature. 2011 Oct 23;480(7376):259-63
references.pmid: 22020280
references.citation: Cell. 2011 Dec 23;147(7):1551-63
references.pmid: 22196730
references.citation: Mol Cell. 2013 Jun 6;50(5):736-48
references.pmid: 23665228
references.citation: Development. 2011 Sep;138(18):4039-50
references.pmid: 21831924
references.citation: Development. 2003 Mar;130(5):859-71
references.pmid: 12538514
references.citation: RNA. 2014 Jun;20(6):773-81
references.pmid: 24757166
references.citation: Nucleic Acids Res. 2014 Jun;42(10):6208-18
references.pmid: 24782529
references.citation: Cell. 2014 Jun 19;157(7):1698-711
references.pmid: 24910301
references.citation: Genes Dev. 2015 Nov 1;29(21):2258-71
references.pmid: 26494711
references.citation: Nature. 2014 May 29;509(7502):633-6
references.pmid: 24828047
references.citation: Genetics. 1995 Feb;139(2):697-711
references.pmid: 7713426
references.citation: Proc Natl Acad Sci U S A. 2011 Dec 27;108(52):21164-9
references.pmid: 22160707
references.citation: RNA. 2013 Jun;19(6):803-10
references.pmid: 23611983
references.citation: Mol Cell. 2008 Sep 26;31(6):785-99
references.pmid: 18922463
references.citation: Genes Dev. 2013 Feb 15;27(4):390-9
references.pmid: 23392610
references.citation: EMBO J. 2014 Sep 17;33(18):1999-2019
references.pmid: 25063675
references.citation: Genes Dev. 2014 Jul 15;28(14):1544-9
references.pmid: 25030694
references.citation: Mol Cell. 2015 Sep 3;59(5):819-30
references.pmid: 26340424
references.citation: Nature. 2012 Nov 8;491(7423):284-7
references.pmid: 23064230
references.citation: Nature. 2006 Jul 13;442(7099):203-7
references.pmid: 16751777
references.citation: Curr Biol. 2011 Aug 23;21(16):1373-9
references.pmid: 21820311
references.citation: Genes Dev. 2015 Mar 15;29(6):617-29
references.pmid: 25762440
references.citation: Nat Struct Mol Biol. 2012 Aug;19(8):773-81
references.pmid: 22842725
references.citation: Nat Cell Biol. 2009 May;11(5):652-8
references.pmid: 19377467
references.citation: Nature. 2011 Nov 27;480(7376):264-7
references.pmid: 22121019
references.citation: Dev Cell. 2003 Aug;5(2):337-50
references.pmid: 12919683
references.citation: Genes Dev. 2007 Jul 1;21(13):1603-8
references.pmid: 17606638
references.citation: Cell Rep. 2014 Jul 10;8(1):103-13
references.pmid: 24953657
references.citation: J Gen Virol. 1997 Sep;78 ( Pt 9):2379-88
references.pmid: 9292028
references.citation: Cell. 2007 Mar 23;128(6):1089-103
references.pmid: 17346786
references.citation: Curr Biol. 2007 Jul 17;17(14):1265-72
references.pmid: 17604629
references.citation: Mol Cell. 2013 Jun 6;50(5):749-61
references.pmid: 23665227
references.citation: PLoS One. 2008 May 21;3(5):e2234
references.pmid: 18493619
references.citation: Aging Cell. 2015 Jun;14(3):443-52
references.pmid: 25754031
references.citation: RNA. 2012 Aug;18(8):1446-57
references.pmid: 22753781
references.citation: Science. 2007 Nov 2;318(5851):761-4
references.pmid: 17975059
references.citation: Curr Biol. 2001 Jul 10;11(13):1017-27
references.pmid: 11470406
references.citation: Cell. 2012 Nov 9;151(4):871-884
references.pmid: 23141543
references.citation: Nature. 2009 Oct 29;461(7268):1296-9
references.pmid: 19812547
references.citation: Cell Res. 2015 Feb;25(2):193-207
references.pmid: 25582079
references.citation: Genes Dev. 2013 Feb 15;27(4):400-12
references.pmid: 23392609
references.citation: Genes Dev. 2014 Aug 1;28(15):1667-80
references.pmid: 25085419
references.citation: Cell. 2009 May 1;137(3):509-21
references.pmid: 19395009
references.citation: Genetics. 2015 Dec;201(4):1381-96
references.pmid: 26482790
references.citation: Mol Cell. 2013 Apr 11;50(1):67-81
references.pmid: 23523368
references.citation: EMBO J. 2013 Jul 3;32(13):1869-85
references.pmid: 23714778
references.citation: Curr Biol. 2010 Apr 27;20(8):724-30
references.pmid: 20362446
references.citation: Mol Cell. 2016 Jan 7;61(1):138-52
references.pmid: 26669262
references.citation: EMBO J. 2010 Oct 6;29(19):3301-17
references.pmid: 20818334
references.citation: Science. 2006 Jul 21;313(5785):320-4
references.pmid: 16809489
references.citation: Development. 2016 Feb 1;143(3):530-9
references.pmid: 26718004
references.citation: Curr Biol. 2009 Dec 29;19(24):2066-76
references.pmid: 20022248
references.citation: Curr Biol. 2011 Nov 22;21(22):1878-87
references.pmid: 22055293
references.citation: Nature. 2012 Oct 4;490(7418):112-5
references.pmid: 22922650
references.citation: Genes Dev. 2015 Jul 1;29(13):1403-15
references.pmid: 26115953
references.citation: Cell Rep. 2015 Aug 18;12(7):1205-16
references.pmid: 26257181
references.citation: Mol Cell. 2011 Sep 16;43(6):1015-22
references.pmid: 21925389
references.citation: Cell Rep. 2015 Apr 21;11(3):366-75
references.pmid: 25865890
references.citation: Genes Dev. 2015 Aug 15;29(16):1747-62
references.pmid: 26302790
references.citation: Science. 2015 May 15;348(6236):817-21
references.pmid: 25977554
references.citation: RNA. 2013 Aug;19(8):1064-77
references.pmid: 23788724
references.citation: RNA. 2012 Jan;18(1):42-52
references.pmid: 22096018
references.citation: Science. 2008 Nov 28;322(5906):1387-92
references.pmid: 19039138
references.citation: EMBO Rep. 2014 Apr;15(4):411-8
references.pmid: 24562610
references.citation: Genes Dev. 2013 Aug 1;27(15):1693-705
references.pmid: 23913922
references.citation: Cell Rep. 2015 Jan 13;10(2):193-203
references.pmid: 25558067
references.citation: Cell Rep. 2015 Jul 21;12(3):429-40
references.pmid: 26166564
references.citation: Annu Rev Genet. 2009;43:467-92
references.pmid: 19919324
references.citation: Science. 2007 Mar 16;315(5818):1587-90
references.pmid: 17322028
references.citation: Mol Cell. 2012 Sep 28;47(6):954-69
references.pmid: 22902557
references.citation: RNA. 2009 Jul;15(7):1258-64
references.pmid: 19460866
references.citation: RNA. 2015 May;21(5):833-9
references.pmid: 25778731
references.citation: Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16325-30
references.pmid: 17056713
references.citation: Cell. 2014 Jun 5;157(6):1353-1363
references.pmid: 24906152
references.citation: EMBO J. 1994 Sep 15;13(18):4401-11
references.pmid: 7925283
references.citation: Mol Cell. 2015 Aug 20;59(4):564-75
references.pmid: 26295961
references.citation: EMBO J. 2009 Dec 16;28(24):3820-31
references.pmid: 19959991
references.citation: Cell. 2012 Nov 21;151(5):964-80
references.pmid: 23159368
references.citation: Mech Dev. 2001 Oct;108(1-2):121-33
references.pmid: 11578866
references.citation: Nature. 2006 Jul 13;442(7099):199-202
references.pmid: 16751776
references.citation: Mol Cell. 2011 Nov 18;44(4):572-84
references.pmid: 22099305
references.citation: Cell. 2009 May 1;137(3):522-35
references.pmid: 19395010
references.citation: EMBO J. 2011 Aug 23;30(19):3977-93
references.pmid: 21863019
references.citation: EMBO J. 2011 Nov 16;30(22):4601-15
references.pmid: 21952049
references.citation: Mol Cell. 2015 Aug 20;59(4):553-63
references.pmid: 26212455
references.citation: Cell Res. 2014 Jun;24(6):680-700
references.pmid: 24787618
references.citation: Mol Cell. 2013 Jun 6;50(5):762-77
references.pmid: 23665231
references.citation: Dev Cell. 2011 Mar 15;20(3):364-75
references.pmid: 21397847
references.citation: Science. 2015 May 15;348(6236):812-817
references.pmid: 25977553
references.citation: Cell Rep. 2015 Aug 25;12(8):1234-43
references.pmid: 26279574
references.citation: Nature. 2012 Nov 8;491(7423):279-83
references.pmid: 23064227
references.citation: Mol Cell. 2014 Dec 4;56(5):708-16
references.pmid: 25453759
references.citation: Genes Dev. 2010 Nov 15;24(22):2493-8
references.pmid: 20966047
references.citation: Elife. 2015 Sep 11;4:
references.pmid: 26359634
references.citation: Cell. 2009 Sep 18;138(6):1137-49
references.pmid: 19732946
references.citation: Genes Dev. 2007 Sep 15;21(18):2300-11
references.pmid: 17875665