An extended wave of global mRNA deadenylation sets up a switch in translation regulation across the mammalian oocyte-to-embryo transition

Without new transcription, gene expression across the oocyte-to-embryo transition (OET) relies instead on regulation of mRNA poly(A) tails to control translation. However, how tail dynamics shape translation across the OET in mammals remains unclear. We perform long -read RNA sequencing to uncover poly(A) tail lengths across the mouse OET and, incorporating published ribosome profiling data, provide an integrated, transcriptome-wide analysis of poly(A) tails and translation across the entire transition. We uncover an extended wave of global deadenylation during fertilization in which short -tailed, oocyte-deposited mRNAs are translationally activated without polyadenylation through resistance to deadenylation. Subsequently, in the embryo, mRNAs are readenylated and translated in a surge of global polyadenylation. We further identify regulation of poly(A) tail length at the isoform level and stage -specific enrichment of mRNA sequence motifs among regulated transcripts. These data provide insight into the stage -specific mechanisms of poly(A) tail regulation that orchestrate gene expression from oocyte to embryo in mammals.