An ancient germ cell-specific RNA-binding protein protects the germline from cryptic splice site poisoning

Ingrid Ehrmann, James H. Crichton, Matthew R. Gazzara, Katherine James, Yilei Liu, Sushma Nagaraja Grellscheid, Tomaž Curk, Dirk de Rooij, Jannetta S. Steyn, Simon Cockell, Ian R. Adams, Yoseph Barash, David J. Elliott

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)
38 Downloads (Pure)

Abstract

Male germ cells of all placental mammals express an ancient nuclear RNA binding protein of unknown function called RBMXL2. Here we find that deletion of the retrogene encoding RBMXL2 blocks spermatogenesis. Transcriptome analyses of age-matched deletion mice show that RBMXL2 controls splicing patterns during meiosis. In particular, RBMXL2 represses the selection of aberrant splice sites and the insertion of cryptic and premature terminal exons. Our data suggest a Rbmxl2 retrogene has been conserved across mammals as part of a splicing control mechanism that is fundamentally important to germ cell biology. We propose that this mechanism is essential to meiosis because it buffers the high ambient concentrations of splicing activators, thereby preventing poisoning of key transcripts and disruption to gene expression by aberrant splice site selection.

Original languageEnglish
Article numbere39304
JournaleLife
Volume8
DOIs
Publication statusPublished - 24 Jan 2019
Externally publishedYes

Keywords

  • alternative splicing
  • chromosomes
  • gene expression
  • meiosis
  • mouse
  • retrogene
  • RNA
  • spermatogenesis

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