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

Authors

Pinhua Wang, Siqi Wang, Haojie Yin, Maosheng Ye, Mingrui Li, Shuai Zhou, Yufeng Wang, Yueshuai Guo, Longfei Jia, Xuejiang Guo, Qiang Wang, Yue Hu, Ran Huo

Published in

Cellular and molecular life sciences : CMLS. Jul 13, 2026. Epub Jul 13, 2026.

Abstract

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, whereas our understanding of repressors' role in this process remains limited in mammals. In our study, we inhibited protein degradation at the 1-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 2-cell stage arrest and failure of ZGA initiation. Moreover, the abnormal accumulation of 4E-T translationally repressed key factors of the 1-cell embryo, including ZBED3 and KDM4A. Mechanistically, the reprsssion is linked to direct interactions of 4E-T with eIF4E and eIF4E1B. These findings suggest that specific maternal RBPs may act as repressors that require precise degradation post-fertilization to relieve translational repression and ensure successful MZT.

PMID:
42440166
Bibliographic data and abstract were imported from PubMed on 13 Jul 2026.

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