SRSF1-mediated alternative splicing is required for spermatogonial stem cell differentiation and mitotic-to-meiotic transition [RNA-Seq]
Alternative splicing (AS) plays significant roles in fundamental biological activities. AS also are prevalent in the testis, but the regulations of alternative splicing in spermatogenesis is vague. Here, we report that Serine/arginine-rich splicing factor 1 (SRSF1), plays critical roles in alternative splicing and male reproduction. Male germ cell-specific deletion of Srsf1 led to complete infertility and abnormal spermatogenesis. We further demonstrated that Srsf1 is required for spermatogonial stem cell differentiation and mitotic-to-meiotic transition. Mechanistically, by combining RNA-seq data with LACE-seq data, we showed that SRSF1 regulatory networks have functions in spermatogenesis. Particularly, we found that SRSF1 affects the AS of Stra8 in a direct manner and Dazl, Dmc1, Mre11a, Syce2 and Rif1 in an indirect manner. Taken together, our findings demonstrate that SRSF1 has crucial functions in spermatogenesis and male fertility by regulating alternative splicing. Overall design: Comparative gene expression profiling analysis of RNA-seq data for Srsf1WT and Srsf1cKO mice testes at P10