The splicing landscape is globally reprogrammed during male meiosis

Claudio Sette, Ralf Schmid, Sushma Nagaraja Grellscheid, Ingrid Ehrmann, Caroline Dalgliesh, Marina Danilenko, Maria Paola Paronetto, Simona Pedrotti, David Grellscheid, Richard J. Dixon, Ian C. Eperon, David J. Elliott

Risultato della ricerca: Contributo in rivistaArticolo in rivista

40 Citazioni (Scopus)

Abstract

Meiosis requires conserved transcriptional changes, but it is not known whether there is a corresponding set of RNA splicing switches. Here, we used RNAseq of mouse testis to identify changes associated with the progression from mitotic spermatogonia to meiotic spermatocytes. We identified ∼150 splicing switches, most of which affect conserved protein-coding exons. The expression of many key splicing regulators changed in the course of meiosis, including downregulation of polypyrimidine tract binding protein (PTBP1) and heterogeneous nuclear RNP A1, and upregulation of nPTB, Tra2β, muscleblind, CELF proteins, Sam68 and T-STAR. The sequences near the regulated exons were significantly enriched in target sites for PTB, Tra2β and STAR proteins. Reporter minigene experiments investigating representative exons in transfected cells showed that PTB binding sites were critical for splicing of a cassette exon in the Ralgps2 mRNA and a shift in alternative 5' splice site usage in the Bptf mRNA. We speculate that nPTB might functionally replace PTBP1 during meiosis for some target exons, with changes in the expression of other splicing factors helping to establish meiotic splicing patterns. Our data suggest that there are substantial changes in the determinants and patterns of alternative splicing in the mitotic-to-meiotic transition of the germ cell cycle.
Lingua originaleEnglish
pagine (da-a)10170-84-10184
RivistaNucleic Acids Research
Volume41
DOI
Stato di pubblicazionePubblicato - 2013

Keywords

  • Alternative Splicing
  • Animals
  • Base Sequence
  • Exons
  • Male
  • Meiosis
  • Mice
  • Molecular Sequence Data
  • RNA Isoforms
  • RNA-Binding Proteins
  • Sequence Analysis, RNA
  • Spermatocytes
  • Spermatogonia
  • Testis
  • Transcriptome

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