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. [Display omitted] •Transcriptome-wide poly(A) tail and translation dynamics from oocyte to embryo in mice•In the oocyte, translation is activated by resistance to global deadenylation•In the embryo, translation is driven by readenylation of stable deadenylated mRNAs•Specific 3′ UTR motifs are associated with poly(A) tail regulation at each stage Lee et al. provide a transcriptome-wide analysis of poly(A) tail and translation dynamics in mice. These data uncover an extended wave of global deadenylation that sets up a switch in translation control, with mRNAs translationally activated by resistance to global deadenylation in the oocyte and by readenylation in the embryo.