IQCH regulates spermatogenesis by interacting with CaM to promote RNA-binding proteins’ expression-Reference-Cited by-同舟云学术

IQCH regulates spermatogenesis by interacting with CaM to promote RNA-binding proteins’ expression

Published:2023-08-29 Issue: Volume: Page:
ISSN:
Container-title:
language:
Short-container-title:

Author:

Ruan Tiechao¹²,Zhou Ruixi¹²,Yang Yihong³,Guo Junchen⁴⁵,Jiang Chuan¹,Wang Xiang¹,Shen Gan¹,Dai Siyu¹,Chen Suren⁶^ORCID,Shen Ying¹

Affiliation:

1. Key Laboratory of Obstetrics, Gynecologic and Pediatric Diseases and Birth Defects of the Ministry of Education, Sichuan University, Chengdu, 610041, China

2. Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041 China

3. Reproduction Medical Center of West China Second University Hospital, Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, Chengdu 610041, China

4. Sichuan University-The Chinese University of Hong Kong (SCU-CUHK) Joint Laboratory for Reproductive Medicine, Key Laboratory of Obstetric, Gynaecologic and Paediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China

5. Reproductive Endocrinology and Regulation Laboratory, Department of Obstetric and Gynaecologic, West China Second University Hospital, Sichuan University, Chengdu 610041, China

6. Education Key Laboratory of Cell Proliferation & Regulation Biology, College of Life Sciences, Beijing Normal University, Beijing 100875, China

Abstract

IQ motif-containing proteins can be recognized by calmodulin (CaM) and are essential for many biological processes. However, the role of IQ motif-containing proteins in spermatogenesis is largely unknown. In this study, we identified a loss-of-function mutation in the novel gene IQ motif-containing H (IQCH) in a Chinese family with male infertility, characterized by a cracked flagellar axoneme and abnormal mitochondrial structure. To verify the function of IQCH, Iqch-knockout mice were generated by CRISPR-Cas9 technology which reproduced the human phenotypes. Mechanistically, IQCH can bind to CaM and then regulate the expression of RNA-binding proteins (especially HNRPAB), which are indispensable for spermatogenesis. Collectively, this study firstly unveiled the function of IQCH, expanded the role of IQ motif-containing proteins in reproductive processes, and provided important guidance for genetic counseling and gene diagnosis for male infertility.

Publisher

eLife Sciences Publications, Ltd