hnRNPH1 in Sertoli cells cooperates with PTBP1 and AR and is essential for spermatogenesis by regulating gene transcription and alternative mRNA splicing

Many RNA binding proteins have been reported to play a role in spermatogenic cells, but their function in Sertoli cells remains largely unclear. Here, we report that hnRNPH1, an RNA binding protein, is highly expressed in Sertoli cells and essential for the maintenance of blood-testis barrier integrity and meiosis. Conditional knockout of hnRNPH1 in mouse Sertoli cells leads to compromised BTB function, delayed meiotic progression, increased germ cell apoptosis, sloughing of germ cells, and eventually infertility of mice. In this study, it was shown that hnRNPH1 could interact with the splicing regulator PTBP1 and regulate the alternative splicing of the target genes functionally related with cell adhesion. On the other hand, hnRNPH1 could cooperate with the AR, one of Sertoli cell-specific transcription factors, to modulate the transcription level of a group of genes associated with cell-cell junction. In addition, some genes involved retinoic acid metabolism and EGFR pathway are also regulated by hnRNPH1. In summary, our findings reveal a crucial role of hnRNPH1 in pre-mRNA alternative splicing and transcriptional regulation in Sertoli cells and provide a new insight for a better understanding of male infertility therapy.