title: Heterotypic piRNA Ping-Pong requires qin, a protein with both E3 ligase and Tudor domains.
abstract: piRNAs guide PIWI proteins to silence transposons in animal germ cells. Reciprocal cycles of piRNA-directed RNA cleavage--catalyzed by the PIWI proteins Aubergine (Aub) and Argonaute3 (Ago3) in Drosophila melanogaster--expand the population of antisense piRNAs in response to transposon expression, a process called the Ping-Pong cycle. Heterotypic Ping-Pong between Aub and Ago3 ensures that antisense piRNAs predominate. We show that qin, a piRNA pathway gene whose protein product contains both E3 ligase and Tudor domains, colocalizes with Aub and Ago3 in nuage, a perinuclear structure implicated in transposon silencing. In qin mutants, less Ago3 binds Aub, futile Aub:Aub homotypic Ping-Pong prevails, antisense piRNAs decrease, many families of mobile genetic elements are reactivated, and DNA damage accumulates in nurse cells and oocytes. We propose that Qin enforces heterotypic Ping-Pong between Aub and Ago3, ensuring that transposons are silenced and maintaining the integrity of the germline genome.
authors.affiliation: Biochemistry and Molecular Pharmacology and Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jia
authors.initials: J
authors.lastname: Xu
authors.forename: Birgit S
authors.initials: BS
authors.lastname: Koppetsch
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Cindy
authors.initials: C
authors.lastname: Tipping
authors.forename: Shengmei
authors.initials: S
authors.lastname: Ma
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Weng
authors.forename: William E
authors.initials: WE
authors.lastname: Theurkauf
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Zamore
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D019295:Computational Biology; D004249:DNA Damage; D004251:DNA Transposable Elements / Q000235:genetics*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005298:Fertility; D020868:Gene Silencing / Q000502:physiology; D049750:Genome, Insect; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000235:genetics; D009154:Mutation; D009865:Oocytes / Q000166:cytology / Q000378:metabolism*; D010053:Ovary / Q000166:cytology / Q000378:metabolism*; D010448:Peptide Initiation Factors / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D059367:RNA Cleavage; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: C518392:AGO3 protein, Drosophila; D060565:Argonaute Proteins; D004251:DNA Transposable Elements; D029721:Drosophila Proteins; D026901:Membrane Transport Proteins; D010448:Peptide Initiation Factors; D034741:RNA, Small Interfering; D034743:RNA-Induced Silencing Complex; C436124:aub protein, Drosophila; C071597:tud protein, Drosophila; C569287:Qin protein, Drosophila; D044767:Ubiquitin-Protein Ligases
references.citation: Curr Biol. 2007 Apr 3;17(7):637-42
references.pmid: 17363252
references.citation: Genetics. 1989 Jan;121(1):101-17
references.pmid: 2492966
references.citation: Mol Cell. 2008 Sep 26;31(6):785-99
references.pmid: 18922463
references.citation: Genes Dev. 2010 Apr 1;24(7):636-46
references.pmid: 20360382
references.citation: Development. 1996 May;122(5):1631-9
references.pmid: 8625849
references.citation: Genes Dev. 1998 Dec 1;12(23):3715-27
references.pmid: 9851978
references.citation: Curr Biol. 2009 Apr 28;19(8):640-4
references.pmid: 19345100
references.citation: Cell. 2009 Sep 18;138(6):1137-49
references.pmid: 19732946
references.citation: Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6714-9
references.pmid: 17428915
references.citation: Science. 2007 May 4;316(5825):744-7
references.pmid: 17446352
references.citation: Genome Res. 2009 Oct;19(10):1776-85
references.pmid: 19541914
references.citation: Genetics. 1984 Aug;107(4):591-610
references.pmid: 6430748
references.citation: Development. 2011 Sep;138(18):4039-50
references.pmid: 21831924
references.citation: Genetics. 1990 Feb;124(2):303-16
references.pmid: 1689686
references.citation: Science. 2007 Jun 15;316(5831):1586-91
references.pmid: 17569856
references.citation: Nature. 2006 Jul 13;442(7099):203-7
references.pmid: 16751777
references.citation: Genes Dev. 2006 Jul 1;20(13):1709-14
references.pmid: 16766680
references.citation: Nat Cell Biol. 2009 May;11(5):652-8
references.pmid: 19377467
references.citation: Genes Dev. 2009 Aug 1;23(15):1749-62
references.pmid: 19584108
references.citation: Genes Dev. 2006 Aug 15;20(16):2214-22
references.pmid: 16882972
references.citation: Nat Rev Genet. 2009 Feb;10(2):94-108
references.pmid: 19148191
references.citation: Science. 2006 Jul 21;313(5785):363-7
references.pmid: 16778019
references.citation: Nucleic Acids Res. 1992 Jul 25;20(14):3731-6
references.pmid: 1322529
references.citation: Genetics. 2007 Apr;175(4):1615-24
references.pmid: 17277359
references.citation: Development. 2008 Jan;135(1):3-9
references.pmid: 18032451
references.citation: Nat Methods. 2011 May;8(5):405-7
references.pmid: 21460824
references.citation: Development. 2000 Feb;127(3):503-14
references.pmid: 10631171
references.citation: Cell. 2007 Mar 23;128(6):1089-103
references.pmid: 17346786
references.citation: J Cell Sci. 2004 Apr 15;117(Pt 10):2109-20
references.pmid: 15090597
references.citation: Nat Methods. 2009 Jun;6(6):431-4
references.pmid: 19465919
references.citation: Nat Genet. 2004 Mar;36(3):288-92
references.pmid: 14981519
references.citation: Curr Biol. 2001 Jul 10;11(13):1017-27
references.pmid: 11470406
references.citation: Nature. 2009 Oct 29;461(7268):1296-9
references.pmid: 19812547
references.citation: Nat Genet. 2004 Mar;36(3):283-7
references.pmid: 14981521
references.citation: Nat Cell Biol. 1999 Oct;1(6):354-7
references.pmid: 10559962
references.citation: Cell. 2009 May 1;137(3):509-21
references.pmid: 19395009
references.citation: PLoS One. 2008 Feb 06;3(2):e1526
references.pmid: 18253480
references.citation: Curr Biol. 2010 Apr 27;20(8):724-30
references.pmid: 20362446
references.citation: Curr Biol. 2002 Oct 1;12(19):1645-51
references.pmid: 12361566
references.citation: Dev Cell. 2007 Jan;12(1):45-55
references.pmid: 17199040
references.citation: Science. 2006 Jul 21;313(5785):320-4
references.pmid: 16809489
references.citation: Curr Biol. 2009 Dec 29;19(24):2066-76
references.pmid: 20022248
references.citation: Nat Rev Mol Cell Biol. 2011 Apr;12(4):246-58
references.pmid: 21427766
references.citation: Nucleic Acids Res. 2005 Feb 24;33(4):e36
references.pmid: 15731329
references.citation: Science. 2008 Nov 28;322(5906):1387-92
references.pmid: 19039138
references.citation: Nucleic Acids Res. 1990 Oct 25;18(20):6097-100
references.pmid: 2172928
references.citation: Nucleic Acids Res. 2005 Jan 1;33(Database issue):D390-5
references.pmid: 15608223
references.citation: Cell. 2007 Apr 6;129(1):69-82
references.pmid: 17418787
references.citation: Nat Methods. 2008 May;5(5):409-15
references.pmid: 18391959
references.citation: Science. 2007 Mar 16;315(5818):1587-90
references.pmid: 17322028
references.citation: Genetics. 1991 Dec;129(4):1119-36
references.pmid: 1783295
references.citation: Development. 2001 Jul;128(14):2823-32
references.pmid: 11526087
references.citation: EMBO J. 2009 Dec 16;28(24):3820-31
references.pmid: 19959991
references.citation: Cold Spring Harb Symp Quant Biol. 2006;71:171-80
references.pmid: 17381294
references.citation: Genetics. 1984 Aug;107(4):611-34
references.pmid: 6430749
references.citation: Mol Cell Biol. 2004 Aug;24(15):6742-50
references.pmid: 15254241
references.citation: Development. 2005 Sep;132(18):4029-39
references.pmid: 16093322
references.citation: Nature. 2006 Jul 13;442(7099):199-202
references.pmid: 16751776
references.citation: Nat Struct Mol Biol. 2007 Apr;14(4):347-8
references.pmid: 17384647
references.citation: Development. 2011 May;138(9):1863-73
references.pmid: 21447556
references.citation: Cell. 2009 May 1;137(3):522-35
references.pmid: 19395010