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

First Author  Takahashi N Year  2023
Journal  Nat Commun Volume  14
Issue  1 Pages  416
PubMed ID  36697412 Mgi Jnum  J:332850
Mgi Id  MGI:7430343 Doi  10.1038/s41467-023-35994-3
Citation  Takahashi N, et al. (2023) CPEB1-dependent disruption of the mRNA translation program in oocytes during maternal aging. Nat Commun 14(1):416
abstractText  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.
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