Germ cell-specific eIF4E1b regulates maternal mRNA translation to ensure zygotic genome activation

Translation of maternal mRNAs is detected before transcription of zygotic genes and is essential for mammalian embryo development. How certain maternal mRNAs are selected for translation instead of degradation and how this burst of translation affects zygotic genome activation remain unknown. Using gene-edited mice, we document that the oocyte-specific eukaryotic translation initiation factor 4E family member 1b (eIF4E1b) is the regulator of maternal mRNA expression that ensures subsequent reprogramming of the zygotic genome. In oocytes, eIF4E1b binds to transcripts encoding translation machinery proteins, chromatin remodelers, and reprogramming factors to promote their translation in zygotes and protect them from degradation. The protein products are thought to establish an open chromatin landscape in one-cell zygotes to enable transcription of genes required for cleavage stage development. Our results define a program for rapid resetting of the zygotic epigenome that is regulated by maternal mRNA expression and provide new insights into the mammalian maternal-to-zygotic transition. In this study, Yang et al. show that the translation initiation factor eIF4E1b protects specific maternal mRNAs and promotes their translation during oocyte-to-zygote transition. This jump-starts critical zygotic chromatin remodeling and genome activation, the loss of which results in female infertility due to developmental arrest in the two-cell embryos.