Primate-Specific DAZ Regulates Translation of Cell Proliferation-Related mRNAs and is Essential for Maintenance of Spermatogonia

Ou, Ningjing1,2,3,4; Wang, Yuci3,4; Xu, Shuai1; Luo, Jiaqiang1; Zhang, Chenwang1; Zhang, Yangyi3,4; Shi, Xiaoyan3,4; Xiong, Minggang3,4; Zhao, Liangyu2; Ji, Zhiyong1; Zhang, Yuxiang1; Zhao, Jingpeng1; Bai, Haowei1; Tian, Ruhui1; Li, Peng1; Zhi, Erlei1; Huang, Yuhua1; Chen, Wei1; Wang, Ruiqi3,4; Jin, Yuxuan3,4; Wang, Dian3,4; Li, Zheng1; Chen, Hao3,4; Yao, Chencheng1

2024-05-01

10.1002/advs.202400692

ADVANCED SCIENCE   影响因子和分区

2198-3844

["Primate-specific DAZ (deleted in azoospermia) has evolved in the azoospermia factor c (AZFc) locus on the Y chromosome. Loss of DAZ is associated with azoospermia in patients with deletion of the AZFc region (AZFc_del). However, the molecular mechanisms of DAZ in spermatogenesis remain uncertain. In this study, the molecular mechanism of DAZ is identified, which is unknown since it is identified 40 years ago because of the lack of a suitable model. Using clinical samples and cell models, it is shown that DAZ plays an important role in spermatogenesis and that loss of DAZ is associated with defective proliferation of c-KIT-positive spermatogonia in patients with AZFc_del. Mechanistically, it is shown that knockdown of DAZ significantly downregulated global translation and subsequently decreased cell proliferation. Furthermore, DAZ interacted with PABPC1 via the DAZ repeat domain to regulate global translation. DAZ targeted mRNAs that are involved in cell proliferation and cell cycle phase transition. These findings indicate that DAZ is a master translational regulator and essential for the maintenance of spermatogonia. Loss of DAZ may result in defective proliferation of c-KIT-positive spermatogonia and spermatogenic failure.","It is revealed that DAZ interacts with PABPC1 via the DAZ repeat domain to regulate the translation of target transcripts involved in cell proliferation and cell cycle phase transition (such as c-KIT and SMC2) in the human testis. Loss of DAZ (Y chromosome AZFc deletion) may result in defective proliferation of c-KIT-positive spermatogonia and spermatogenic failure. image"]

DAZ microdeletion of AZFc proliferation RNA binding protein spermatogenic failure

SCI ; EI

英语

通讯

National Key R&D Program of China[2022YFC2702705] ; National Key Research and Development Program of China[32170604] ; National Natural Science Foundation of China[2021QN02Y122] ; Pearl River Recruitment Program of Talents[20231120115406001] ; Shenzhen Science and Technology Program[B2021032]

Chemistry ; Science & Technology - Other Topics ; Materials Science

Chemistry, Multidisciplinary ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary

WOS:001229895700001

WILEY

Web of Science

1.Shanghai Jiao Tong Univ, Sch Med, Shanghai Gen Hosp, Dept Androl,Ctr Mens Hlth,Urol Med Ctr, Shanghai 200011, Peoples R China
2.Sun Yat sen Univ, Affiliated Hosp 5, Dept Urol, Dept Intervent Med,Guangdong Prov Key Lab Biomed I, Zhuhai 519000, Guangdong, Peoples R China
3.Southern Univ Sci & Technol, Sch Med, Dept Human Cell Biol & Genet, Joint Lab Guangdong, Shenzhen 518000, Guangdong, Peoples R China
4.Southern Univ Sci & Technol, Hong Kong Univ Vasc Homeostasis & Dis, Sch Med, Shenzhen 518000, Guangdong, Peoples R China

Ou, Ningjing,Wang, Yuci,Xu, Shuai,et al. Primate-Specific DAZ Regulates Translation of Cell Proliferation-Related mRNAs and is Essential for Maintenance of Spermatogonia[J]. ADVANCED SCIENCE,2024.

Ou, Ningjing.,Wang, Yuci.,Xu, Shuai.,Luo, Jiaqiang.,Zhang, Chenwang.,...&Yao, Chencheng.(2024).Primate-Specific DAZ Regulates Translation of Cell Proliferation-Related mRNAs and is Essential for Maintenance of Spermatogonia.ADVANCED SCIENCE.

Ou, Ningjing,et al."Primate-Specific DAZ Regulates Translation of Cell Proliferation-Related mRNAs and is Essential for Maintenance of Spermatogonia".ADVANCED SCIENCE (2024).