hnRNPH1: Modulating transcription, splicing and crosstalk in the testis

In the testis, crosstalk between Sertoli cells (SCs) and germ cells is essential for spermatogenesis, as is the formation of the blood-testis barrier (BTB), composed of specialised junctions between SCs. The molecular mechanisms underlying both these processes are incompletely understood. Shuiqiao Yuan and colleagues have previously uncovered a role for the RNA-binding protein hnRNPH1 in regulating alternative splicing in germ cells, and now set out to determine whether this protein is also required in SCs. They find that male mice lacking Hnrnph1 in SCs are completely infertile, with spermatogenesis being impaired at late stages and the BTB being disrupted. They further show that hnRNPH1 interacts directly with the splicing factor PTBP1 to regulate alternative splicing of a number of transcripts, including genes involved in cell-cell junction formation. They further show that hnRNPH1 regulates gene expression at the transcriptional level, via interaction with the androgen receptor (AR). Since AR signalling in SCs is required for meiotic progression of germ cells, this provides a potential mechanism by which Hnrnph1 deletion affects spermatogenesis. These findings add to our understanding of the crosstalk between SCs and germ cells, and underscore the importance of post-transcriptional regulation in this system.