CPEB1-dependent disruption of the mRNA translation program in oocytes during maternal aging.

Nozomi Takahashi, Federica Franciosi, Enrico Maria Daldello, Xuan G Luong, Peter Althoff, Xiaotian Wang, Marco Conti

Nature communications 2023 Jan 26

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The molecular causes of deteriorating oocyte quality during aging are poorly defined. Since oocyte developmental competence relies on post-transcriptional regulations, we tested whether defective mRNA translation contributes to this decline in quality. Disruption in ribosome loading on maternal transcripts is present in old oocytes. Using a candidate approach, we detect altered translation of 3'-UTR-reporters and altered poly(A) length of the endogenous mRNAs. mRNA polyadenylation depends on the cytoplasmic polyadenylation binding protein 1 (CPEB1). Cpeb1 mRNA translation and protein levels are decreased in old oocytes. This decrease causes de-repression of Ccnb1 translation in quiescent oocytes, premature CDK1 activation, and accelerated reentry into meiosis. De-repression of Ccnb1 is corrected by Cpeb1 mRNA injection in old oocytes. Oocyte-specific Cpeb1 haploinsufficiency in young oocytes recapitulates all the translation phenotypes of old oocytes. These findings demonstrate that a dysfunction in the oocyte translation program is associated with the decline in oocyte quality during aging. © 2023. The Author(s).

Citation

Nozomi Takahashi, Federica Franciosi, Enrico Maria Daldello, Xuan G Luong, Peter Althoff, Xiaotian Wang, Marco Conti. CPEB1-dependent disruption of the mRNA translation program in oocytes during maternal aging. Nature communications. 2023 Jan 26;14(1):416