Ewsr1b, Syncrip, HuR and alternative 3'UTRs 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 identified sequential waves of translation critical for proper development progression. The first wave occurred within 1 h and included translation of ewsr1b mRNA that harbored a short 3' untranslated region (UTR) comprising 16 nucleotides. The resulting Ewsr1b protein triggered the second translation wave through binding cytoplasmic mRNAs, including pou5f3, which encodes a transcription factor promoting zygotic genome activation. In contrast, HuR and Syncrip repressed translation until the first and second waves, respectively. ewsr1b mRNA that had a long 3'UTR was translated in the second wave, and the 3'UTRs length determined 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.