Guangdong and Shenzhen Key Laboratory of Reproductive Medicine and Genetics, The Center of Reproductive Medicine, Peking University Shenzhen Hospital, 1120 Lianhua Rd, Futian District, Shenzhen, 518000, China.
CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
BMC Biol. 2023 Oct 23;21(1):231. doi: 10.1186/s12915-023-01736-6.
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.
RNA 剪接在基本的生物活动中起着重要的作用。然而，我们对在精子发生过程中可变剪接的作用和潜在机制的了解是有限的。
在这里，我们报告丝氨酸/精氨酸丰富的剪接因子 2（SRSF2），也称为 SC35，在可变剪接和男性生殖中起着关键作用。Stra8-Cre 介导的 Srsf2 雄性生殖细胞特异性缺失导致完全不育和精子发生缺陷。进一步的分析表明，Srsf2 的缺失破坏了精原细胞的分化和减数分裂起始。在机制上，我们将 RNA-seq 数据与 LACE-seq 数据相结合，表明 SRSF2 调控网络在几个主要事件中起着关键作用，包括生殖发育、精子发生、减数分裂细胞周期、突触组织、DNA 重组、染色体分离和男性性别分化。此外，SRSF2 直接影响 Stra8、Stag3 和 Atr 的表达和可变剪接，这些基因编码精子发生的关键因子。
综上所述，我们的研究结果表明，SRSF2 通过调节可变剪接在精子发生和男性生育力中具有重要功能。
