Post-transcriptional repression of mRNA enhances competence to transit from mitosis to meiosis in mouse spermatogenic cells.

ABSTRACT

The special cell cycle known as meiosis transforms diploid germ cells into haploid gametes. In mammalian testes, diploid spermatogenic cells become competent to transition from mitosis to meiosis in response to retinoic acid. In mice, previous studies revealed that MEIOC, alongside binding partners YTHDC2 and RBM46, represses mitotic genes and promotes robust meiotic gene expression in spermatogenic cells that have already initiated meiosis. Here, we molecularly dissect MEIOC-dependent regulation in mouse spermatogenic cells and find that MEIOC actually shapes the transcriptome much earlier, even before meiotic initiation. MEIOC, acting with YTHDC2 and RBM46, destabilizes mRNA targets, including transcriptional repressors E2f6 and Mga, in mitotic spermatogonia. MEIOC thereby derepresses E2F6- and MGA-repressed genes, including Meiosin and other meiosis-associated genes. This confers on spermatogenic cells the molecular competence to, in response to retinoic acid, fully activate the STRA8-MEIOSIN transcriptional regulator, which is required for the meiotic G1/S cell cycle transition and meiotic gene expression. We conclude that in mice, mRNA decay mediated by MEIOC-YTHDC2-RBM46 enhances the competence of mitotic spermatogonia to transit from mitosis to meiosis.