SRSF2 is required for mRNA splicing and spermatogenesis [RNA-seq]

Serine/arginine-rich splicing factor 2 (SRSF2), also known as SC35, is a member of a SRs protein family, which plays significant roles in numerous fundamental biological activities. However, the roles and underlying mechanisms of SRSF2 remain largely unclear during spermatogenesis. Here, we report that SRSF2 is involved in alternative splicing and that male germ cell-specific deletion of Srsf2 by Stra8-GFPCre causes absolute infertility and defective spermatogenesis. Further analyses revealed that deletion of Srsf2 in the male germ cells had harmful influences on the differentiation of spermatogonia and meiosis initiation. Mechanistically, by combining RNA-seq data with LACE-seq data, we showed that spermatogenesis, meiotic cell cycle, male gamete generation, reproductive development, and male sex differentiation were involved in the SRSF2 regulatory networks. Furthermore, SRSF2 affects expression and AS of Stra8, Stag3 and Atr in a direct manner, which were critical factors during spermatogenesis. Taken together, our results demonstrate that SRSF2 has important functions in spermatogenesis and male fertility by regulating alternative splicing. Comparative gene expression profiling analysis of RNA-seq data for Srsf2WT and Srsf2cKO mice testes at P10富含丝氨酸/精氨酸剪接因子2（SRSF2，亦称SC35）是SR蛋白家族的一员，在众多基础生物学活动中发挥关键作用。然而，SRSF2在精子发生过程中的具体作用与潜在机制仍有待阐明。本研究显示，SRSF2参与可变剪接调控；利用Stra8-GFPCre介导的雄性生殖细胞特异性敲除Srsf2，可导致雄性小鼠完全不育，并引发精子发生缺陷。进一步分析表明，雄性生殖细胞中Srsf2的缺失会对精原细胞分化与减数分裂起始产生不利影响。机制层面，通过联合RNA测序（RNA-seq）与LACE-seq数据，我们发现精子发生、减数分裂细胞周期、雄性配子发生、生殖发育以及雄性性别分化等生物学过程均处于SRSF2的调控网络之中。此外，SRSF2可直接调控精子发生关键因子Stra8、Stag3与Atr的表达及可变剪接事件。综上，本研究结果证实，SRSF2通过调控可变剪接在精子发生与雄性生育能力中发挥重要功能。本研究还对出生后第10天（P10）的Srsf2野生型（Srsf2WT）与Srsf2条件性敲除（Srsf2cKO）小鼠睾丸的RNA-seq数据开展了比较基因表达谱分析。