1. Guangdong and Shenzhen Key Laboratory of Reproductive Medicine and Genetics, The Center of Reproductive Medicine, Peking University Shenzhen Hospital, Shenzhen 518000, China.
2. Department of Urology & Andrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China.
3. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
4. School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing, 100049, China.
5. Guangzhou Key Laboratory of Metabolic Diseases and Reproductive Health, Guangdong-Hongkong Metabolism & Reproduction Joint Laboratory, Reproductive Medicine Center, Guangdong Second Provincial General Hospital, Guangzhou, 510317, China.
6. Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA.
7. Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, 100101, China.
8. CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
†These authors contributed equally to this work.
Alternative splicing (AS) plays significant roles in a multitude of fundamental biological activities. AS is prevalent in the testis, but the regulations of AS in spermatogenesis is only little explored. 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 by affecting spermatogenesis. Mechanistically, by combining RNA-seq data with LACE-seq data, we showed that SRSF1 affected the AS of Stra8 in a direct manner and Dazl, Dmc1, Mre11a, Syce2 and Rif1 in an indirect manner. Our findings demonstrate that SRSF1 has crucial functions in spermatogenesis and male fertility by regulating alternative splicing.
Keywords: SRSF1, male infertility, alternative splicing, spermatogenesis