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

哺乳动物卵母细胞向胚胎转变过程中,一波持续的全球性mRNA去腺苷酸化作用引发了翻译调控的转变。

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作者:Katherine Lee ,Kyucheol Cho ,Robert Morey ,Heidi Cook-Andersen

Abstract

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. Keywords: 3′ UTR motif; CP: Developmental biology; CP: Molecular biology; deadenylation; development; mRNA stability; oocyte-to-embryo transition; polyadenylation; post-transcriptional regulation; translation.

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