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- Title
Human-specific gene CT47 blocks PRMT5 degradation to lead to meiosis arrest.
- Authors
Li, Chao; Feng, Yuming; Fu, Zhenxin; Deng, Junjie; Gu, Yue; Wang, Hanben; Wu, Xin; Huang, Zhengyun; Zhu, Yichen; Liu, Zhiwei; Huang, Moli; Wang, Tao; Hu, Shijun; Yao, Bing; Zeng, Yizhun; Zhou, Chengji J.; Brown, Steve D. M.; Liu, Yi; Vidal-Puig, Antonio; Dong, Yingying
- Abstract
Exploring the functions of human-specific genes (HSGs) is challenging due to the lack of a tractable genetic model system. Testosterone is essential for maintaining human spermatogenesis and fertility, but the underlying mechanism is unclear. Here, we identified Cancer/Testis Antigen gene family 47 (CT47) as an essential regulator of human-specific spermatogenesis by stabilizing arginine methyltransferase 5 (PRMT5). A humanized mouse model revealed that CT47 functions to arrest spermatogenesis by interacting with and regulating CT47/PRMT5 accumulation in the nucleus during the leptotene/zygotene-to-pachytene transition of meiosis. We demonstrate that testosterone induces nuclear depletion of CT47/PRMT5 and rescues leptotene-arrested spermatocyte progression in humanized testes. Loss of CT47 in human embryonic stem cells (hESCs) by CRISPR/Cas9 led to an increase in haploid cells but blocked the testosterone-induced increase in haploid cells when hESCs were differentiated into haploid spermatogenic cells. Moreover, CT47 levels were decreased in nonobstructive azoospermia. Together, these results established CT47 as a crucial regulator of human spermatogenesis by preventing meiosis initiation before the testosterone surge.
- Subjects
MEIOSIS; SPERMATOGENESIS; HUMAN embryonic stem cells; PROTEIN arginine methyltransferases; GENETIC models
- Publication
Cell Death Discovery, 2022, Vol 8, Issue 1, p1
- ISSN
2058-7716
- Publication type
Article
- DOI
10.1038/s41420-022-01139-6