A mechanism of target mRNA selection and activity regulation in meiosis-related RBM46-MEIOC-YTHDC2 complex.

MEIOC and its two partners, RBM46 and YTHDC2, function as posttranscriptional regulators to promote mitotic-to-meiotic transition in mammalian germ cells. However, the molecular mechanism underlying target mRNA selection and degradation by MEIOC complex is largely unknown. Here, we demonstrate that exogenously expressed RBM46/MEIOC/YTHDC2 binds to Rad21 and Meioc 3'UTR and targets these transcripts for degradation in cultured somatic cells. YTHDC2 stabilizes MEIOC through inhibiting its ubiquitination, and the coiled-coil domain of MEIOC mediates its association with YTHDC2 and RBM46. The target mRNA is required for the interaction of RBM46 with YTHDC2. Moreover, MEIOC recruits XRN2 in the cytoplasm as the likely ribonuclease. We propose that MEIOC is a critical component that recruits RNA binding proteins for target mRNA selection and XRN2 for RNA degradation, and regulates the complex activity by modulating its mRNA and protein stability.