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小鼠卵母细胞成熟过程中普遍存在的3'-UTR异构体转换

Pervasive 3'-UTR Isoform Switches During Mouse Oocyte Maturation.

作者信息

He Yuanlin, Chen Qiuzhen, Zhang Jing, Yu Jing, Xia Meng, Wang Xi

机构信息

State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.

Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.

出版信息

Front Mol Biosci. 2021 Oct 18;8:727614. doi: 10.3389/fmolb.2021.727614. eCollection 2021.

Abstract

Oocyte maturation is the foundation for developing healthy individuals of mammals. Upon germinal vesicle breakdown, oocyte meiosis resumes and the synthesis of new transcripts ceases. To quantitatively profile the transcriptomic dynamics after meiotic resumption throughout the oocyte maturation, we generated transcriptome sequencing data with individual mouse oocytes at three main developmental stages: germinal vesicle (GV), metaphase I (MI), and metaphase II (MII). When clustering the sequenced oocytes, results showed that isoform-level expression analysis outperformed gene-level analysis, indicating isoform expression provided extra information that was useful in distinguishing oocyte stages. Comparing transcriptomes of the oocytes at the GV stage and the MII stage, in addition to identification of differentially expressed genes (DEGs), we detected many differentially expressed transcripts (DETs), some of which came from genes that were not identified as DEGs. When breaking down the isoform-level changes into alternative RNA processing events, we found the main source of isoform composition changes was the alternative usage of polyadenylation sites. With detailed analysis focusing on the alternative usage of 3'-UTR isoforms, we identified, out of 3,810 tested genes, 512 (13.7%) exhibiting significant switches of 3'-UTR isoforms during the process of moues oocyte maturation. Altogether, our data and analyses suggest the importance of examining isoform abundance changes during oocyte maturation, and further investigation of the pervasive 3'-UTR isoform switches in the transition may deepen our understanding on the molecular mechanisms underlying mammalian early development.

摘要

卵母细胞成熟是哺乳动物发育健康个体的基础。在生发泡破裂后,卵母细胞减数分裂恢复,新转录本的合成停止。为了定量分析整个卵母细胞成熟过程中减数分裂恢复后的转录组动态变化,我们在三个主要发育阶段生成了单个小鼠卵母细胞的转录组测序数据:生发泡(GV)、中期I(MI)和中期II(MII)。对测序的卵母细胞进行聚类时,结果表明异构体水平的表达分析优于基因水平的分析,这表明异构体表达提供了有助于区分卵母细胞阶段的额外信息。比较GV期和MII期卵母细胞的转录组,除了鉴定差异表达基因(DEG)外,我们还检测到许多差异表达转录本(DET),其中一些来自未被鉴定为DEG的基因。当将异构体水平的变化分解为可变RNA加工事件时,我们发现异构体组成变化的主要来源是聚腺苷酸化位点的可变使用。通过对3'-UTR异构体可变使用的详细分析,我们在3810个测试基因中鉴定出512个(13.7%)在小鼠卵母细胞成熟过程中表现出3'-UTR异构体的显著转换。总之,我们的数据和分析表明在卵母细胞成熟过程中检查异构体丰度变化的重要性,对这一转变中普遍存在的3'-UTR异构体转换的进一步研究可能会加深我们对哺乳动物早期发育分子机制的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13b6/8558312/05b03f7c0f48/fmolb-08-727614-g001.jpg

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