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. |