<i>Cpeb1</i> expression is post‐transcriptionally regulated by AUF1, CPEB1, and microRNAs

Oe, Souichi; Hayashi, S.; Tanaka, Susumu; Koike, Taro; Hirahara, Yukie; Kakizaki, Rio; Sakamoto, Sumika; Noda, Yasuko; Yamada, Hisao; Kitada, Masaaki

doi:10.1002/2211-5463.13286

Cited by 4 publications

(3 citation statements)

References 37 publications

(48 reference statements)

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“…8 ) and represses its own translation in GV oocytes 57 . Moreover, an element that binds AU-rich binding factor 1 (AUF1) has been described, and a function for microRNA-dependent modulation of Cpeb1 has been described in neuroblastoma cells 58 . Thus, several possible mechanisms may be causing a decreased translation of Cpeb1 during oocyte growth and maturation, mechanisms that require further investigation.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2023

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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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Section: Discussionmentioning

confidence: 99%

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

et al. 2023

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“…However, these PPP-related mRNAs are not effectively degraded in the in vitro environment, highlighting a key difference in embryonic development under these two conditions. This could be due to variations in the expression of genes involved in mRNA degradation, particularly those binding to mRNAs, such as CPEB1 [60]. Additionally, it is important to note that within the CNOT (CCR4-NOT transcription complex) subunits-specifically CNOT7, CNOT6L, and CNOT11, compared to CNOT1/2/3/4/6/8/9/10 from minor ZGA to major ZGA-similar functions may be undertaken by different subunits at various stages, such as CNOT6 and CNOT8 [61].…”

Section: Discussionmentioning

confidence: 99%

Single-Cell RNA Sequencing Reveals Differences in Chromatin Remodeling and Energy Metabolism among In Vivo-Developed, In Vitro-Fertilized, and Parthenogenetically Activated Embryos from the Oocyte to 8-Cell Stages in Pigs

Fan,

Liu,

Zhao

et al. 2024

Animals

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In vitro-fertilized (IVF) and parthenogenetically activated (PA) embryos, key to genetic engineering, face more developmental challenges than in vivo-developed embryos (IVV). We analyzed single-cell RNA-seq data from the oocyte to eight-cell stages in IVV, IVF, and PA porcine embryos, focusing on developmental differences during early zygotic genome activation (ZGA), a vital stage for embryonic development. (1) Our findings reveal that in vitro embryos (IVF and PA) exhibit more similar developmental trajectories compared to IVV embryos, with PA embryos showing the least gene diversity at each stage. (2) Significant differences in maternal mRNA, particularly affecting mRNA splicing, energy metabolism, and chromatin remodeling, were observed. Key genes like SMARCB1 (in vivo) and SIRT1 (in vitro) played major roles, with HDAC1 (in vivo) and EZH2 (in vitro) likely central in their complexes. (3) Across different types of embryos, there was minimal overlap in gene upregulation during ZGA, with IVV embryos demonstrating more pronounced upregulation. During minor ZGA, global epigenetic modification patterns diverged and expanded further. Specifically, in IVV, genes, especially those linked to H4 acetylation and H2 ubiquitination, were more actively regulated compared to PA embryos, which showed an increase in H3 methylation. Additionally, both types displayed a distinction in DNA methylation. During major ZGA, IVV distinctively upregulated genes related to mitochondrial regulation, ATP synthesis, and oxidative phosphorylation. (4) Furthermore, disparities in mRNA degradation-related genes between in vivo and in vitro embryos were more pronounced during major ZGA. In IVV, there was significant maternal mRNA degradation. Maternal genes regulating phosphatase activity and cell junctions, highly expressed in both in vivo and in vitro embryos, were degraded in IVV in a timely manner but not in in vitro embryos. (5) Our analysis also highlighted a higher expression of many mitochondrially encoded genes in in vitro embryos, yet their nucleosome occupancy and the ATP8 expression were notably higher in IVV.

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“…In addition, IL8 expression is regulated by several distinct mechanisms through the 3′-UTR since there exist multiple binding sites of trans-acting factors, such as miR-93-5p [ 30 ], miR-520c-3p [ 31 ], HuR [ 32 ], KSRP [ 13 ]. Therefore, the possibility that JNJ-7706621 administration prevented the interaction between AUF1 and IL8 mRNA but activated other pathways to inhibit IL8 expression [ 33 , 34 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

A Novel Strategy for Regulating mRNA’s Degradation via Interfering the AUF1’s Binding to mRNA

Sun

et al. 2022

Molecules

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The study on the mechanism and kinetics of mRNA degradation provides a new vision for chemical intervention on protein expression. The AU enrichment element (ARE) in mRNA 3′-UTR can be recognized and bound by the ARE binding protein (AU-rich Element factor (AUF1) to recruit RNase for degradation. In the present study, we proposed a novel strategy for expression regulation that interferes with the AUF1-RNA binding. A small-molecule compound, JNJ-7706621, was found to bind AUF1 protein and inhibit mRNA degradation by screening the commercial compound library. We discovered that JNJ-7706621 could inhibit the expression of AUF1 targeted gene IL8, an essential pro-inflammatory factor, by interfering with the mRNA homeostatic state. These studies provide innovative drug design strategies to regulate mRNA homeostasis.

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Cpeb1 expression is post‐transcriptionally regulated by AUF1, CPEB1, and microRNAs

Cited by 4 publications

References 37 publications

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

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

Single-Cell RNA Sequencing Reveals Differences in Chromatin Remodeling and Energy Metabolism among In Vivo-Developed, In Vitro-Fertilized, and Parthenogenetically Activated Embryos from the Oocyte to 8-Cell Stages in Pigs

A Novel Strategy for Regulating mRNA’s Degradation via Interfering the AUF1’s Binding to mRNA

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