Alternative 3′ UTRs and RNA-binding proteins Ewsr1b, HuR, and Syncrip organize sequential waves of translation to drive embryonic development

Eggs of many species accumulate thousands of dormant mRNAs that are translated after fertilization at specific times and locations to direct development. However, how embryos coordinate translation of these mRNAs remains unclear. In this study, we identify sequential waves of translation critical for proper development progression. The first wave occurs within 1 h and includes translation of ewsr1b mRNA that harbors a short 3' untranslated region (UTR) comprising 16 nucleotides. The resulting Ewsr1b protein triggers the second translation wave through binding cytoplasmic mRNAs, including pou5f3, which encodes a transcription factor promoting zygotic genome activation. In contrast, HuR and Syncrip repress translation until the first and second waves, respectively. ewsr1b mRNA that has a long 3' UTR is translated in the second wave, and the 3' UTR's length determines protein localization and function. Overall, our findings reveal previously unknown molecular principles that coordinate translation timings and protein functions to drive long-term, multilayered processes.