PT - JOURNAL ARTICLE AU - Wen-Long Lei AU - Zongchang Du AU - Tie-Gang Meng AU - Ruibao Su AU - Yuan-Yuan Li AU - Wenbo Liu AU - Si-Min Sun AU - Meng-Yu Liu AU - Yi Hou AU - Chun-Hui Zhang AU - Yaoting Gui AU - Heide Schatten AU - Zhiming Han AU - Chenli Liu AU - Zhen-Bo Wang AU - Wei-Ping Qian AU - Qing-Yuan Sun TI - SRSF2 is required for mRNA splicing and spermatogenesis AID - 10.1101/2022.09.20.508723 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.09.20.508723 4099 - http://biorxiv.org/content/early/2022/09/21/2022.09.20.508723.short 4100 - http://biorxiv.org/content/early/2022/09/21/2022.09.20.508723.full AB - RNA splicing plays significant roles in fundamental biological activities. However, our knowledge about the roles of alternative splicing and underlying mechanisms during spermatogenesis is limited. Here, we report that Serine/arginine-rich splicing factor 2 (SRSF2), also known as SC35, plays critical roles in alternative splicing and male reproduction. Male germ cell-specific deletion of Srsf2 by Stra8-Cre caused complete infertility and defective spermatogenesis. Further analyses revealed that deletion of Srsf2 disrupted differentiation and meiosis initiation of spermatogonia. Mechanistically, by combining RNA-seq data with LACE-seq data, we showed that SRSF2 regulatory networks play critical roles in several major events including reproductive development, spermatogenesis, meiotic cell cycle, synapse organization, DNA recombination, chromosome segregation, and male sex differentiation. Furthermore, SRSF2 affected expression and alternative splicing of Stra8, Stag3 and Atr encoding critical factors for spermatogenesis in a direct manner. Taken together, our results demonstrate that SRSF2 has important functions in spermatogenesis and male fertility by regulating alternative splicing.Competing Interest StatementThe authors have declared no competing interest.