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 via CRISPR-Cas9 technology, which reproduced human phenotypes. Mechanistically, IQCH can bind to CaM and subsequently regulate the expression of RNA-binding proteins (especially HNRPAB), which are indispensable for spermatogenesis. Overall, this study revealed the function of IQCH, expanded the role of IQ motif-containing proteins in reproductive processes, and provided important guidance for genetic counseling and genetic diagnosis of male infertility.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
According to the reviewers' comments, we have added detailed methods for the IP protocol used in the LC-MS/MS analysis and ensured consistent terminology for LC-MS/MS throughout the revised manuscript. We have also included the method for RNA-binding protein immunoprecipitation and corrected the spelling errors.
