Blockade of Pachytene piRNA Biogenesis Reveals a Novel Requirement for Maintaining Post-Meiotic Germline Genome Integrity 英文参考文献.docVIP

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Blockade of Pachytene piRNA Biogenesis Reveals a Novel Requirement for Maintaining Post-Meiotic Germline Genome Integrity 英文参考文献.doc

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Blockade of Pachytene piRNA Biogenesis Reveals a Novel Requirement for Maintaining Post-Meiotic Germline Genome Integrity 英文参考文献

BlockadeofPachytenepiRNABiogenesisRevealsaNovel RequirementforMaintainingPost-MeioticGermline GenomeIntegrity KeZheng,P.JeremyWang* Department of Animal Biology, Center for Animal Transgenesis and Germ Cell Research, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania,UnitedStatesofAmerica Abstract Piwi-interactingRNAsareadiverseclassofsmallnon-codingRNAsimplicatedinthesilencingoftransposableelementsand thesafeguardingofgenomeintegrity.Inmammals,malegermcellsexpresstwogeneticallyanddevelopmentallydistinct populations of piRNAs at the pre-pachytene and pachytene stages of meiosis, respectively. Pre-pachytene piRNAs are mostlyderivedfromretrotransposonsandrequiredfortheirsilencing.Incontrast,pachytenepiRNAsoriginatefrom,3,000 genomicclusters,andtheirbiogenesisandfunctionremainenigmatic.Here,wereportthatconditionalinactivationofthe putative RNA helicase MOV10L1 in mouse spermatocytes produces a specific loss of pachytene piRNAs, significant accumulation of pachytene piRNA precursor transcripts, and unusual polar conglomeration of Piwi proteins with mitochondria. Pachytene piRNA–deficient spermatocytes progress through meiosis without derepression of LINE1 retrotransposons,butbecomearrestedatthepost-meioticroundspermatidstagewithmassiveDNAdamage.Ourresults demonstratethatMOV10L1actsupstreamofPiwiproteinsintheprimaryprocessingofpachytenepiRNAsandsuggestthat, distinct from pre-pachytene piRNAs, pachytene piRNAs fulfill a unique function in maintaining post-meiotic genome integrity. Citation: Zheng K, Wang PJ (2012) Blockade of Pachytene piRNA Biogenesis Reveals a Novel Requirement for Maintaining Post-Meiotic Germline Genome Integrity.PLoSGenet8(11):e1003038.doi:10.1371/journal.pgen.1003038 Editor:JohnC.Schimenti,CornellUniversity,UnitedStatesofAmerica ReceivedMarch16,2012;AcceptedSeptember5,2012;PublishedNovember15,2012 Copyright: ? 2012 Zheng, Wang. This is an open-access article distributed under the terms of the Creative Commons Att