MicroRNA-202 safeguards meiotic progression by preventing premature degradation of REC8 mediated by separase

MicroRNAs (miRNAs) are believed to play important roles in mammalian spermatogenesis but the in vivo functions of single miRNAs in this highly complex developmental process remain unclear. Here, we reported that miR-202, a member of the let-7 family, played an important role in mouse spermatogenesis by phenotypic evaluation of miR-202 knockout (KO) mice. In miR-202 KO mice, germ cells underwent apoptosis. Multiple processes in meiosis I including synapsis and crossover formation were disrupted, and inter-sister chromatid synapses were detected. More importantly, we found that upon miR-202 KO, meiotic-specific cohesin protein REC8 was prematurely cleaved by precociously activated separase, whose mRNA was a direct target of miR-202-3p. Our findings identify miR-202 as a novel regulator of meiosis and contribute to the list of miRNAs that play specific and important roles in developmental processes.