title: RNF17 blocks promiscuous activity of PIWI proteins in mouse testes.
abstract: PIWI proteins and their associated piRNAs protect germ cells from the activity of mobile genetic elements. Two classes of piRNAs—primary and secondary—are defined by their mechanisms of biogenesis. Primary piRNAs are processed directly from transcripts of piRNA cluster loci, whereas secondary piRNAs are generated in an adaptive amplification loop, termed the ping-pong cycle. In mammals, piRNA populations are dynamic, shifting as male germ cells develop. Embryonic piRNAs consist of both primary and secondary species and are mainly directed toward transposons. In meiotic cells, the piRNA population is transposon-poor and largely restricted to primary piRNAs derived from pachytene piRNA clusters. The transition from the embryonic to the adult piRNA pathway is not well understood. Here we show that RNF17 shapes adult meiotic piRNA content by suppressing the production of secondary piRNAs. In the absence of RNF17, ping-pong occurs inappropriately in meiotic cells. Ping-pong initiates piRNA responses against not only transposons but also protein-coding genes and long noncoding RNAs, including genes essential for germ cell development. Thus, the sterility of Rnf17 mutants may be a manifestation of a small RNA-based autoimmune reaction.
authors.affiliation: Watson School of Biological Sciences, Cold Spring Harbor Laboratory, New York 11724, USA; Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York 11724, USA;
authors.forename: Kaja A
authors.initials: KA
authors.lastname: Wasik
authors.affiliation: Watson School of Biological Sciences, Cold Spring Harbor Laboratory, New York 11724, USA;
authors.forename: Oliver H
authors.initials: OH
authors.lastname: Tam
authors.affiliation: Watson School of Biological Sciences, Cold Spring Harbor Laboratory, New York 11724, USA; Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York 11724, USA;
authors.forename: Simon R
authors.initials: SR
authors.lastname: Knott
authors.affiliation: Watson School of Biological Sciences, Cold Spring Harbor Laboratory, New York 11724, USA; Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York 11724, USA;
authors.forename: Ilaria
authors.initials: I
authors.lastname: Falciatori
authors.affiliation: Watson School of Biological Sciences, Cold Spring Harbor Laboratory, New York 11724, USA;
authors.forename: Molly
authors.initials: M
authors.lastname: Hammell
authors.affiliation: Watson School of Biological Sciences, Cold Spring Harbor Laboratory, New York 11724, USA; Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York 11724, USA;
authors.forename: Vasily V
authors.initials: VV
authors.lastname: Vagin
authors.affiliation: Watson School of Biological Sciences, Cold Spring Harbor Laboratory, New York 11724, USA; Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York 11724, USA; Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, United Kingdom.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Hannon
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism*; D004251:DNA Transposable Elements / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D055786:Gene Knockout Techniques; D008297:Male; D008540:Meiosis / Q000235:genetics; D051379:Mice; D009154:Mutation; D034741:RNA, Small Interfering / Q000378:metabolism; D013737:Testis / Q000378:metabolism / Q000503:physiopathology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D060565:Argonaute Proteins; D004251:DNA Transposable Elements; D034741:RNA, Small Interfering; C402374:Rnf17 protein, mouse; D014157:Transcription Factors
keywords: PIWI proteins; germ cells; piRNAs; spermatogenesis; transposons