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母源 mRNA 去腺苷酸化在体外成熟的小鼠和人卵母细胞中存在缺陷。

Maternal mRNA deadenylation is defective in in vitro matured mouse and human oocytes.

机构信息

College of Life Science, Northeast Forestry University, Harbin, 150040, China.

State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China.

出版信息

Nat Commun. 2024 Jul 2;15(1):5550. doi: 10.1038/s41467-024-49695-y.

Abstract

Oocyte in vitro maturation is a technique in assisted reproductive technology. Thousands of genes show abnormally high expression in in vitro maturated metaphase II (MII) oocytes compared to those matured in vivo in bovines, mice, and humans. The mechanisms underlying this phenomenon are poorly understood. Here, we use poly(A) inclusive RNA isoform sequencing (PAIso-seq) for profiling the transcriptome-wide poly(A) tails in both in vivo and in vitro matured mouse and human oocytes. Our results demonstrate that the observed increase in maternal mRNA abundance is caused by impaired deadenylation in in vitro MII oocytes. Moreover, the cytoplasmic polyadenylation of dormant Btg4 and Cnot7 mRNAs, which encode key components of deadenylation machinery, is impaired in in vitro MII oocytes, contributing to reduced translation of these deadenylase machinery components and subsequently impaired global maternal mRNA deadenylation. Our findings highlight impaired maternal mRNA deadenylation as a distinct molecular defect in in vitro MII oocytes.

摘要

卵母细胞体外成熟是辅助生殖技术中的一种技术。与体内成熟的牛、鼠和人卵母细胞相比,体外成熟的中期 II(MII)卵母细胞中数千个基因表现出异常高的表达。目前,人们对这种现象的机制还知之甚少。在这里,我们使用聚(A)包含的 RNA 异构体测序(PAIso-seq)来分析体内和体外成熟的小鼠和人类卵母细胞的转录组范围的 poly(A)尾。我们的研究结果表明,在体外 MII 卵母细胞中观察到的母体 mRNA 丰度增加是由于去腺苷酸化受损所致。此外,休眠的 Btg4 和 Cnot7 mRNA 的细胞质多聚腺苷酸化受损,这些 mRNA 编码去腺苷酸化机制的关键成分,导致这些去腺苷酸酶机制成分的翻译减少,随后母体 mRNA 去腺苷酸化受损。我们的研究结果强调了体外 MII 卵母细胞中母体 mRNA 去腺苷酸化受损是一种明显的分子缺陷。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57b4/11219934/0d0bb1710cf3/41467_2024_49695_Fig1_HTML.jpg

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