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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 and Marco Conti ()
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Nozomi Takahashi: University of California
Federica Franciosi: University of California
Enrico Maria Daldello: University of California
Xuan G. Luong: University of California
Peter Althoff: University of California
Xiaotian Wang: University of California
Marco Conti: University of California

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-35994-3

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