The degradation of maternal RNA-binding protein 4E-T regulates translational activation to ensure maternal-to-zygotic transition in mouse embryos

The maternal-to-zygotic transition (MZT) is essential for early embryonic development, comprising zygotic genome activation (ZGA) as well as the degradation of maternal RNAs and proteins. Current research on MZT has primarily focused on the maternal activators, while the role of repressors in this process remains largely unexplored. In our study, we inhibited protein degradation at the one-cell stage using the proteasome inhibitor MG132 and observed impaired pre-implantation development and defective ZGA. Proteomic analysis of MG132-treated embryos showed that significantly up-regulated proteins in abundance were enriched for RNA-binding proteins (RBPs). Further functional screening highlighted one critical factor, 4E-T (EIF4ENIF1), whose overexpression caused two-cell stage arrest and failure of ZGA initiation. Moreover, the abnormal accumulation of 4E-T repressed translational activation and decreased ZBED3, KDM4A, etc., key factors expression in 1-cell embryo, which connected with interactions of 4E-T with eIF4E and eIF4E1B. These findings suggest that specific maternal RBP may act as repressors that require precise degradation post-fertilization to relieve translational repression and ensure successful MZT.