PABPN1 couples the polyadenylation and translation of maternal transcripts to mouse oocyte meiotic maturation
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ABSTRACT:
PROVIDER: PRJNA1157193 | ENA |
REPOSITORIES: ENA
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Project description:In the process of mammalian maternal-to-zygotic transition (MZT), the degradation of zygotic decay (Z-decay) mRNA is later than that of maternal factor-mediated mRNA decay (M-decay) mRNA. The regulatory mechanism and physiological significance of Z-decay mRNA to maintain stability during meiosis are urgent scientific questions. In this study, we identified that PAPα worked together with poly(A)-bound RNA binding protein PABPN1 to promote the polyadenylation and translation of maternal transcripts, leading to rupture of germinal vesicles in mammalian oocytes. The oocytes specifically knocked out Pabpn1 at the primary follicle stage could develop into the fully grown (FGO) stage, but hardly could enter to the meiotic process. Furthermore, PABPN1 maintains the stability of Z-decay maternal transcripts during oocyte meiotic maturation. A number of Z-decay transcripts and the translational activity in Pabpn1-null oocytes was significantly lower than that of wild-type oocytes during meiosis. Therefore, during meiotic maturation of oocytes, PABPN1 maintains the stability of Z-decay transcripts and promotes the degradation of some M-decay transcripts, ensuring normal GVBD and polar body-1 emission.
2025-07-02 | GSE276390 | GEO
Project description:Poly(A) polymerase α (PAPα), as the specific mRNA polyadenylation enzyme in the cytoplasm of mammalian oocytes, is essential for oocytes to exclude the first polar body. However, PAPα knockout did not affect germinal vesicles breakdown (GVBD) of oocytes, and the mechanism needs to be further explored. In this study, we identified that PAPα work together with poly(A)-bound RNA binding protein PABPN1 to promote the rupture of germinal vesicles in mammalian oocytes. The protein level of Pabpn1 gradually increases with the meiotic maturation of oocytes. The oocytes specifically knocked out Pabpn1 at the primary follicle stage could develop into the fully grown (FGO) stage, but hardly could enter into the meiotic process. The activated form of CDK1 was injected into Pabpn1-null oocytes, the oocytes could enter into meiotic process. The translational activity of Pabpn1-null oocytes was significantly lower than that of wild-type oocytes during meiosis. In particular, the expression level of protein (BTG4 and CDC25), which were essential for the meiotic maturation of oocytes, were significantly decreased. Therefore, during the oocyte meiosis process, PABPN1 and PAPα jointly promote the oocyte to enter the meiosis process.
2022-08-23 | GSE184028 | GEO
Project description:Nuclear mRNA metabolism is regulated by multiple proteins, which either directly bind to RNA or form multi-protein complexes. The RNA-binding protein ZC3H11A is involved in nuclear mRNA export, and NF-κB signaling and is essential during mouse embryo development. Furthermore, previous studies have shown that ZC3H11A is important for nuclear-replicating viruses. However, detailed biochemical characterization of the ZC3H11A protein has been lacking. In this study, we established the ZC3H11A protein interactome in human and mouse cells. We demonstrate that the nuclear poly(A)-binding protein PABPN1 interacts specifically with the ZC3H11A protein and controls ZC3H11A localization into nuclear speckles. We report that ZC3H11A specifically interacts with the human adenovirus type 5 (HAdV-5) capsid mRNA in a PABPN1-dependent manner. Notably, ZC3H11A uses the same zinc finger motifs to interact with PABPN1 and mRNA, with a single zinc finger motif responsible for these functions. Further, we demonstrate that the lack of ZC3H11A alters the polyadenylation of HAdV-5 capsid mRNA. Taken together, our results suggest that the ZC3H11A protein acts as a novel regulator of polyadenylation of nuclear mRNA.
2023-10-24 | PXD042238 | Pride
Project description:CNOT6L Couples the Selective Degradation of Maternal Transcriptsto Meiotic Cell Cycle Progression in Mouse Oocyte
| PRJNA486092 | ENA
Project description:PARP12 regulates mouse oocyte meiotic maturation
| PRJNA961639 | ENA
Project description:Purpose: The goals of this study are to study the function of Cnot6l during oocyte maturation and the differences between loss of Cnot6l and Btg4 during oocyte maturation. Methods:Comparing the degration of transcripts at different stage in WT, Btg4-/- and Cnot6l-/- oocytes by RNA sequencing. Results: Using an optimized data analysis workflow, we mapped about 15 million sequence reads per sample to the mouse genome (build mm9) and identified 23236 transcripts with TopHat workflow. Conclusions: CNOT6L stimulated degradation of maternal transcriptsto oocyte meiotic maturation.
2018-11-23 | GSE118562 | GEO
Project description:The growing oocytes stored a large amount of maternal mRNA to support the subsequent "maternal-zygotic transition" process, which is a key regulatory events in female reproduction. The accumulation of maternal mRNA in the growing oocyte determines the developmental potential of the oocyte. At present, it is not clear how the growing oocytes store and process the newly transcribed mRNA under physiological conditions, including the distribution and localization of mRNA in the oocyte, as well as the molecular mechanism and physiological significance of this localization. In this study, we found that poly(A) tailed mRNA has the dynamic distributions of droplet fusion and gradual disappearance in the mouse nucleus as oocyte growth and meiotic maturation. Our research found that PABPN1 modulated the dynamic compartmentalization of mRNA with poly(A) tails to form NmPD (nuclear mRNA processing domain) during the growing oocytes through phase separation. The NmPD in Pabpn1-null oocytes could not form the compartmentalized distribution, and the Pabpn1 knockout females were sterile with defects of premature ovarian failure. Combined with multi-omics sequencing analysis, we investigate that NmPD was essential for long 3'-UTR isoform formation and the stability of mRNA in growing oocytes.
2021-07-06 | GSE179406 | GEO
Project description:Purpose: The goals of this study are to study the function of Cnot6l during oocyte maturation . Methods: Comparing the polysome-bounded transcripts at GV, MI and MII stage in WT and Cnot6l-/- oocytes by RNA sequencing. Results: Using an optimized data analysis workflow, we mapped about 15 million sequence reads per sample to the mouse genome (build mm9) and identified 23236 transcripts with TopHat workflow. Conclusions: CNOT6L stimulated degradation of maternal transcriptsto oocyte meiotic maturation.
2018-11-23 | GSE118563 | GEO
Project description:PABPN1 promotes meiotic maturation of oocytes by interacting with PAPOLA
| PRJNA762877 | ENA
Project description:Polyadenylation controls mRNA biogenesis, nuclear export, translation, and decay. These processes are interdependent and coordinately regulated by poly(A)-binding proteins (PABPs), yet how PABPs are themselves regulated is not fully understood. Here, we show that human PABPN1, the nuclear PABP, is phosphorylated by mitotic kinases at four specific sites during mitosis, a time when nucleoplasm and cytoplasm mix. Phospho-inhibitory mutations decreased human cell proliferation. We therefore employed long-read sequencing to determine how PABPN1 phospho-site mutants affected poly(A) tails lengths of individual mRNAs, and TimeLapse-seq to monitor mRNA synthesis and decay. Phospho-inhibitory PABPN1 mutants lengthened poly(A) tails on both spliced and unspliced transcripts. In contrast, expression of phospho-mimetic PABPN1 resulted in shorter poly(A) tails and reduced transcriptome stability, indicating reduced polyadenylation activity of PABPN1 and targeting of long-tailed transcripts for decay. Thus, PABPN1 phosphorylation confers transcriptome instability that is associated with resetting the gene expression program as cells passage through cell cycle.
2024-06-26 | GSE247007 | GEO