CPEB1-dependent disruption of the mRNA translation program in oocytes during maternal aging
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ABSTRACT:
PROVIDER: PRJNA922940 | ENA |
REPOSITORIES: ENA
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Project description: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.
2023-01-11 | GSE222638 | GEO
Project description: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.
| S-EPMC9877008 | biostudies-literature
Project description:In vertebrates, sexual reproduction depends on the precisely temporally controlled translation of mRNAs stockpiled in the oocyte. The RNA-binding proteins Zar1 and Zar2 have been implicated in translational control in oocytes of several vertebrate species, but how they act mechanistically is still incompletely understood. Here, we investigate the function of Zar1l, a so far uncharacterized member of the Zar protein family, in Xenopus laevis oocytes. By combining biochemical assays and mass spectrometry, we reveal that Zar1l is a constituent of a known large ribonucleoparticle containing the translation repressor 4E-T and the central polyadenylation regulator CPEB1. Employing TRIM-Away, we show that depletion of Zar1l from prophase-I arrested oocytes results in premature meiotic maturation upon hormone treatment. We provide evidence that this is based on the precocious expression of the kinase cMos, a key promotor of meiotic resumption. Based on our data, we propose a model according to which degradation of Zar1l results in dissociation of 4E-T from CPEB1, thus weakening translation inhibition imposed by the mRNA 3’UTR of cMos and probably also other M-phase promoting regulators. Thus, our detailed characterization of the function of Zar1l reveals novel mechanistic insights into the regulation of maternal mRNA translation during vertebrate meiosis.
2022-09-22 | PXD032170 | Pride
Project description:CPEB1 regulates cellular function by post-transcriptionally controlling its targeted transcripts' translation. After bound to CPEs, CPEB1 recruits cytoplasmic poly (A) polymerase GLD2 to elongate the poly (A) tail for the maintenance of mRNA stability. The stability of mRNA is positively correlated with translational output. It is unexamined whether CPEB1 interacts with translation machinery to regulation translation. Previous reports demonstrate that phosphorylation is required for its regulation on translation. However, it is not well understood whether phosphorylation is essential for CPEB1 interaction with translation machinery or not. Here, we performed mass spectrometry on C2 cells transfected with CPEB1-mVenus or CPEB1 (T171A, S177A)-mVenus after IgG or mVenus antibody immunoprecipitation. After analysis, we identify CPEB1 interacting proteins and the phosphorylation dependent interacting proteins such as ribosomal proteins. Thus, our data suggest that CPEB1 regulate translation by interacting with translation machinery in a phosphorylation dependent manner.
2021-11-04 | PXD020822 | Pride
Project description:CPEB1-4 RIP-Seq in S.VI Xenopus laevis oocytes [RIP-seq]
| PRJNA783542 | ENA
Project description:Cytoplasmic polyadenylation element binding protein 1 (CPEB1) regulates polyadenylation and subsequent translation of CPE-containing mRNAs, which contributes to various physiological and pathological phenomena. To clarify changes in gene expression profiles caused by dysregulation of CPEB1 expression, we performed microarray analyses and revealed that reduced CPEB1 expression altered the expression levels of numerous genes. These findings indicate that accurate post-transcriptional regulation of CPEB1 expression contributes to the maintenance of global gene expression partially through modulating lncRNA expression.
2021-03-31 | GSE147604 | GEO
Project description:Sequencial functions of CPEB1 and CPEB4 in the localization of repressed mRNAs to the mitotic spindle and their subsequent phase-specific activation to promote cell phase transitions and correct chromosome segregation
2018-02-15 | GSE100764 | GEO
Project description:Pancreatic cancer is a leading cause of cancer death worldwide. Cytoplasmic polyadenylation element binding protein 1 (CPEB1) is a fundamental translation regulatory factor regulating the polyadenylation process of messenger RNA. However, its biological functions in pancreatic cancer are poorly understood. Here the CPEB1 gene was knocked down or overexpressed in JF-305 cell line. To investigate the role of CPEB1 and new interacting proteins, proteomic analysis was performed using LC-MS/MS approach.
2024-07-03 | PXD047241 | Pride
Project description:Here we show sequential functions of CPEB1 and CPEB4 in the localization of repressed mRNAs to the mitotic spindle and their subsequent phase -specific activation to promote cell phase transitions and correct chromosome segregation.
2021-06-29 | GSE99810 | GEO
Project description:To identify CPEB1 and CPEB4 regulated RNA we performed CPEB1 and CPEB4 RNA immunoprecipitation (RIP) followed by microarray hybridization analysis with striatal (St) RNA from wild-type (WT) and R6/1 mice (HD mice).
2020-03-06 | GSE113833 | GEO