Two sequential waves of mRNA translation drive embryonic development

Global and local controls of protein syntheses in cells and organisms are crucial for driving diverse biological processes. Eggs accumulate thousands of dormant mRNAs that are translated after fertilization at specific times and locations to direct development. However, molecular systems that coordinate temporal and spatial translation in long-term, multilayered processes remain unclear. In this study, we identified two sequential waves of translation critical for proper development progression. The first wave occurred within 1 h after fertilization and included translation of ewsr1b mRNA, which encodes an RNA-binding protein Ewsr1b. The resulting Ewsr1b protein promoted the second translation wave through binding to cytoplasmic mRNAs, including pou5f3 mRNA, which encodes a transcription factor essential for development. In contrast, an RNA-binding protein Syncrip accumulated in eggs and repressed pou5f3 mRNA translation until the second wave. Notably, ewsr1b mRNA translated in the first wave harbored a short 3′ untranslated region (UTR) comprising 16 nucleotides, whereas ewsr1b mRNA translated in the second wave had a long 3′UTR comprising 302 nucleotides. This difference determined not only translational timing but also Ewsr1b’s localization and function. Overall, our findings reveal previously unknown molecular principles for coordinating translation timing, protein function, and embryonic development.