CWF19L2 is Essential for Male Fertility and Spermatogenesis by Regulating Alternative Splicing

Autor: Shiyu Wang, Yuling Cai, Tongtong Li, Yan Wang, Ziyou Bao, Renxue Wang, Junchao Qin, Ziqi Wang, Yining Liu, Zhaojian Liu, Wai‐Yee Chan, Xiangfeng Chen, Gang Lu, Zi‐Jiang Chen, Tao Huang, Hongbin Liu
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Advanced Science, Vol 11, Iss 31, Pp n/a-n/a (2024)
Druh dokumentu: article
ISSN: 2198-3844
DOI: 10.1002/advs.202403866
Popis: Abstract The progression of spermatogenesis along specific developmental trajectories depends on the coordinated regulation of pre‐mRNA alternative splicing (AS) at the post‐transcriptional level. However, the fundamental mechanism of AS in spermatogenesis remains to be investigated. Here, it is demonstrated that CWF19L2 plays a pivotal role in spermatogenesis and male fertility. In germline conditional Cwf19l2 knockout mice exhibiting male sterility, impaired spermatogenesis characterized by increased apoptosis and decreased differentiated spermatogonia and spermatocytes is observed. That CWF19L2 interacted with several spliceosome proteins to participate in the proper assembly and stability of the spliceosome is discovered. By integrating RNA‐seq and LACE‐seq data, it is further confirmed CWF19L2 directly bound and regulated the splicing of genes related to spermatogenesis (Znhit1, Btrc, and Fbxw7) and RNA splicing (Rbfox1, Celf1, and Rbm10). Additionally, CWF19L2 can indirectly amplify its effect on splicing regulation through modulating RBFOX1. Collectively, this research establishes that CWF19L2 orchestrates a splicing factor network to ensure accurate pre‐mRNA splicing during the early steps of spermatogenesis.
Databáze: Directory of Open Access Journals
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