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Int J Biol Sci 2023; 19(15):4883-4897. doi:10.7150/ijbs.83474 This issue Cite

Research Paper

SRSF1-mediated alternative splicing is required for spermatogenesis

Wen-Long Lei^1,2†, Yuan-Yuan Li^3†, Zongchang Du^4†, Ruibao Su^5†, Tie-Gang Meng⁵, Yan Ning³, Guanmei Hou³, Heide Schatten⁶, Zhen-Bo Wang^3,7, Zhiming Han^3,7, Fei Sun^2✉, Wei-Ping Qian^1✉, Chenli Liu^8✉, Qing-Yuan Sun^5✉

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.

✉ Corresponding authors: Department of Urology & Andrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, #3 Qingchun East Road, Shangcheng District, Hangzhou, 310016, China. E-mail: sunfeisrrshedu.cn (Fei 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. Tel/Fax: +8675583923333-5213; E-mail: qianweipingszcom (Wei-Ping Qian); CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, 1068 Xueyuan Avenue, Nanshan District, Shenzhen 518055, China. Tel/Fax: +86755 86392288; E-mail: cl.liuac.cn (Chenli Liu); Reproductive Medicine Center, Guangdong Second Provincial General Hospital, #466 Xin-Gang-Zhong-Lu, Haizhu District, Guangzhou 510317, China. Tel: +862089169839; E-mail: sunqyorg.cn (Qing-Yuan Sun). More

Abstract

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

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