An ancient testis-specific IQ motif containing H gene regulates specific isoform expression during spermatogenesis

ABSTRACT: Spermatogenic cells express more alternatively spliced RNAs than most whole tissues; however, the regulation of these events remains unclear. Here we characterize the function of a testis-specific IQ motif containing H gene (Iqch), whose expression has been confirmed to be testis specific in all mammalian species analyzed yet its role remains elusive. Using a mutant mouse model, we found that Iqch is essential for the specific expression of RNA isoforms during spermatogenesis. Through immunohistochemistry of adult mouse testis, we noted that Iqch was localized in somatic and germ cells, including spermatogonia, spermatocytes and round spermatids. Further, Iqch was expressed mainly in the nucleus at the stages spermatocyte and spermatid, where IQCH appeared juxtaposed with SRRM2 and ERSP1, suggesting that interactions among these proteins regulate alternative splicing (AS). By RNA-seq, we noted that mutant Iqch produces alterations in gene expression, including the clear downregulation of testis-specific lncRNAs and protein coding genes at the spermatid stage, and AS modifications, principally increased intron retention, resulting in complete male infertility. Interestingly, the presence of WT Iqch allowed us to identify novel spliced transcripts, while mutant Iqch modified the expression and use of hundreds of RNA isoforms, favoring the expression of the canonical form. This suggests that Iqch is part of a splicing control mechanism, essential in germ cell biology. Our findings reveal the role of Iqch in spermatogenesis and provide clues to the molecular mechanisms controlling the expression of RNA isoforms, mainly in the last stages of spermatogenesis

ORGANISM(S): Mus musculus

PROVIDER: GSE214201 | GEO | 2023/03/22

REPOSITORIES: GEO