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.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
We have checked and simplified IQCH-associated GO functions, and have revised the graphical representation and layout of Figure 5 in revised manuscript. We also have supplemented negative controls in all Co-IP experiments and provided band sizes, and have provided the results of LC-MS/MS experiment analysis in new Data S1 in revised manuscript. Furthermore, we have modified descriptions about the results of Sanger sequencing based on HGVS nomenclature. Moreover, we have modified the title of the study, have revised the inaccuracies and grammatical errors throughout the manuscript, and also have added description of the context to avoid the confusion.
