An ancient testis-specific IQ motif containing H gene regulates specific transcript 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) using a mutant mouse model. We found that Iqch is essential for the specific expression of RNA isoforms during spermatogenesis. Through immunohistochemistry of testis, we noted that Iqch was expressed mainly in the nucleus of spermatocyte and spermatid, where IQCH appeared juxtaposed with SRRM2 and ERSP1 in the nuclear speckles, 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, we have identified novel spliced transcripts in the WT testis, 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.