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

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.