The splicing landscape is globally reprogrammed during male meiosis

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

Research output: Contribution to journalArticlepeer-review

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 proteincoding exons. The expression of many key splicing regulators changed in the course ofmeiosis, 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, Tra2b 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 themitotic-to-meiotic transition of the germ cell cycle.

Original languageEnglish
Pages (from-to)10170-10184
Number of pages15
JournalNucleic Acids Research
Volume41
Issue number22
DOIs
Publication statusPublished - Dec 2013

ASJC Scopus subject areas

  • Genetics

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