Endocrine Abstracts

Accurate posttranscriptional regulation of gene expression is essential for the production of good quality spermatozoa. Active cell type-specific transcription, exceptionally diverse transcriptome, and finally, near-to-complete transcriptional silencing during the late steps of spermatogenesis create a high demand for effective RNA regulatory mechanisms. Furthermore, RNAs packed inside spermatozoa can mediate epigenetic inheritance of father’s acquired disorders, therefore having important implications on offspring health. Male germ cells are characterized by intriguing cytoplasmic ribonucleoprotein granules (germ granules) that participate in RNA regulation during spermatogenesis. By molecular characterization of germ granules in mice, we have revealed their central role in germline-specific RNA regulation. We have shown that in addition to the PIWI-interacting RNA (piRNA) pathway, germ granules in haploid male germ cells accumulate the components of the nonsense mediated mRNA decay (NMD) pathway. The NMD acts mainly by promoting the degradation of mRNAs undergoing premature translation termination, but it can also regulate the stability of a variety of other kind of substrates. Using germ cell-specific knockout mouse models, we have shown that the NMD-targeted RNA degradation is required for normal spermatogenesis, and has a critical role in the control of male germ cell’s transcriptome. Altogether our results emphasize the significance of germ granule-associated RNA quality control mechanisms in the maintenance of male fertility.