Lookup NU author(s): Dr Sushma Grellscheid,
Dr Ingrid Ehrmann,
Dr Marina Danilenko,
Professor David Elliott
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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 similar to 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, Tra2 beta, muscleblind, CELF proteins, Sam68 and T-STAR. The sequences near the regulated exons were significantly enriched in target sites for PTB, Tra2 beta 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.
Author(s): Schmid R, Grellscheid SN, Ehrmann I, Dalgliesh C, Danilenko M, Paronetto MP, Pedrotti S, Grellscheid D, Dixon RJ, Sette C, Eperon IC, Elliott DJ
Publication type: Article
Publication status: Published
Journal: Nucleic Acids Research
Print publication date: 01/12/2013
ISSN (print): 0305-1048
ISSN (electronic): 1362-4962
Publisher: Oxford University Press
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