Destabilization of mRNAs enhances competence to initiate meiosis in mouse spermatogenic cells.

The specialized cell cycle of meiosis transforms diploid germ cells into haploid gametes. In mammals, diploid spermatogenic cells acquire the competence to initiate meiosis in response to retinoic acid. Previous mouse studies revealed that MEIOC interacts with RNA-binding proteins YTHDC2 and RBM46 to repress mitotic genes and promote robust meiotic gene expression in spermatogenic cells that have initiated meiosis. Here, we used the enhanced resolution of scRNA-seq, and bulk RNA-seq of developmentally synchronized spermatogenesis, to define how MEIOC molecularly supports early meiosis in spermatogenic cells. We demonstrate that MEIOC mediates transcriptomic changes before meiotic initiation, earlier than previously appreciated. MEIOC, acting with YTHDC2 and RBM46, destabilizes its mRNA targets, including transcriptional repressors SUMMARY STATEMENT: RNA-binding complex MEIOC-YTHDC2-RBM46 destabilizes its mRNA targets, including transcriptional repressors. This activity facilitates the retinoic acid-dependent activation of