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Ubiquitination-Deficient Mutations in Human Piwi Cause Male Infertility by Impairing Histone-to-Protamine Exchange During Spermiogenesis 期刊论文

编号：

4244b69d-6ea4-4a9a-902a-b535cf741b1a
作者：

Gou, LanTao^[1,7];Kang, JunYan^[1];Dai, Peng^[1];Wang, Xin^[1];Li, Feng^[1];Zhao, Shuang^[1];Zhang, Man^[2];Hua, MinMin^[1,3];Lu, Yi^[3];Zhu, Yong^[4];Li, Zheng^[4];Chen, Hong(陈红)^[5]Wu, LiGang^[1];Li, Dangsheng^[6];Fu, XiangDong^[7];Li, Jinsong^[2,8];Shi, HuiJuan^[3];Liu, MoFang^[1,8,9];
语种：

英文
期刊：

OBSTETRICAL & GYNECOLOGICAL SURVEY ISSN：0029-7828 2017 年 72 卷 9 期 (540 - 541) ; SEP
收录：
摘要：

Genetic studies in worms, flies, fish, and mice indicate that the evolutionarily conserved Piwi proteins are specifically expressed during the development of the animal germline and are essential for gametogenesis in animals. Vertebrate Piwi proteins includeMIWI in mice and HIWI in humans. The human genome encodes Piwi proteins that are mainly expressed in testis; their potential function in human germline development and male infertility is unclear. A previous study identified a conserved destruction box (D-box) as a hotspot for mutations that may be a cause of male infertility in mice and humans.
A recent study suggested that elimination of MIWI through ubiquitination of histones (mediated by the ubiquitin ligase RNF8) is a key initial step in spermatogenesis. How this occurs and whether it is triggered at a defined developmental stage of spermatogenesis remain unknown.
The authors report germline mutations in the D-box region of the human Piwi (Hiwi) gene in patients with idiopathic azoospermia that prevent its ubiquitination and degradation. Through modeling of such mutations in Piwi (Miwi) knockin mice, it was demonstrated that during late spermiogenesis D-boxmutations directly contribute tomale infertility by binding of MIWI with the histone ubiquitin ligase RNF8 (in the cytoplasm of spermatids) in a Piwi-interacting, RNA-independent manner. Use of an RNF8-N-peptide fragment, which impairs the interaction between endogenous RNF8 and MIWI, functionally rescues defective spermiogenesis.
These findings provide direct evidence for cytoplasmic sequestration of RNF8 byMIWI as a key disease event. In late-stage spermiogenesis, histone retention, abnormal morphology, and severely compromised activity in the aberrant sperm can be functionally rescued through blocking RNF8-MIWI interaction in spermatids with an RNF8-N peptide.
The overall data identify Piwi as a causitive factor in human infertility and show its role in regulating the histone-toprotamine exchange during spermiogenesis. The results in the mouse model suggest that D-box mutations are likely disease drivers in humans.
推荐引用方式
GB/T 7714：

Gou Lan-Tao,Kang Jun-Yan,Dai Peng, et al. Ubiquitination-Deficient Mutations in Human Piwi Cause Male Infertility by Impairing Histone-to-Protamine Exchange During Spermiogenesis [J].OBSTETRICAL & GYNECOLOGICAL SURVEY,2017,72(9):540-541.
APA：

Gou Lan-Tao,Kang Jun-Yan,Dai Peng,Wang Xin,&Liu Mo-Fang.(2017).Ubiquitination-Deficient Mutations in Human Piwi Cause Male Infertility by Impairing Histone-to-Protamine Exchange During Spermiogenesis .OBSTETRICAL & GYNECOLOGICAL SURVEY,72(9):540-541.
MLA：

Gou Lan-Tao, et al. "Ubiquitination-Deficient Mutations in Human Piwi Cause Male Infertility by Impairing Histone-to-Protamine Exchange During Spermiogenesis" .OBSTETRICAL & GYNECOLOGICAL SURVEY 72,9(2017):540-541.

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