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.
BMC biology. 2023 Oct 23*** epublish ***
Wen-Long Lei, Zongchang Du, Tie-Gang Meng, Ruibao Su, Yuan-Yuan Li, Wenbo Liu, Si-Min Sun, Meng-Yu Liu, Yi Hou, Chun-Hui Zhang, Yaoting Gui, Heide Schatten, Zhiming Han, Chenli Liu, Fei Sun, Zhen-Bo Wang, Wei-Ping Qian, Qing-Yuan Sun
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., School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing, 100049, China., Fertility Preservation Lab, Guangdong-Hongkong Metabolism & Reproduction Joint Laboratory, Reproductive Medicine Center, Guangdong Second Provincial General Hospital, #466 Xin-Gang-Zhong-Lu, Haizhu District, Guangzhou, 510317, China., State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, #1 Beichen West Road, Chaoyang District, Beijing, 100101, China., Department of Obstetrics and Gynecology, Center for Reproductive Medicine/Department of Fetal Medicine and Prenatal Diagnosis/BioResource Research Center, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China., Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen, 518036, China., Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, 65211, USA., CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China., Department of Urology & Andrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, #3 Qingchun East Road, Shangcheng District, Hangzhou, 310016, China. ., State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, #1 Beichen West Road, Chaoyang District, Beijing, 100101, China. ., 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. ., Fertility Preservation Lab, Guangdong-Hongkong Metabolism & Reproduction Joint Laboratory, Reproductive Medicine Center, Guangdong Second Provincial General Hospital, #466 Xin-Gang-Zhong-Lu, Haizhu District, Guangzhou, 510317, China. .