RNF17 blocks promiscuous activity of PIWI proteins in mouse testes

Genes Dev. 2015 Jul 1;29(13):1403-15. doi: 10.1101/gad.265215.115. Epub 2015 Jun 26.

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.

Keywords: PIWI proteins; germ cells; piRNAs; spermatogenesis; transposons.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Argonaute Proteins / genetics
  • Argonaute Proteins / metabolism*
  • DNA Transposable Elements / genetics
  • Gene Expression Regulation, Developmental / genetics*
  • Gene Knockout Techniques
  • Male
  • Meiosis / genetics
  • Mice
  • Mutation
  • RNA, Small Interfering / metabolism
  • Testis / metabolism
  • Testis / physiopathology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Argonaute Proteins
  • DNA Transposable Elements
  • RNA, Small Interfering
  • Rnf17 protein, mouse
  • Transcription Factors