NAT10-mediated mRNA N 4 -acetylation is essential for the translational regulation during oocyte meiotic maturation in mice

IF 11.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Science Advances Pub Date : 2025-02-21 DOI:10.1126/sciadv.adp5163
Lu Chen, Wen-Jing Wang, Shao-Yuan Liu, Rui-Bao Su, Yu-Ke Wu, Xuan Wu, Song-Ying Zhang, Jie Qiao, Qian-Qian Sha, Heng-Yu Fan
{"title":"NAT10-mediated mRNA N 4 -acetylation is essential for the translational regulation during oocyte meiotic maturation in mice","authors":"Lu Chen, Wen-Jing Wang, Shao-Yuan Liu, Rui-Bao Su, Yu-Ke Wu, Xuan Wu, Song-Ying Zhang, Jie Qiao, Qian-Qian Sha, Heng-Yu Fan","doi":"10.1126/sciadv.adp5163","DOIUrl":null,"url":null,"abstract":"The precise translational regulation of maternal messenger RNAs (mRNAs) drives mammalian oocyte maturation. However, the function and mechanism of posttranscriptional chemical modifications, especially the newly identified <jats:italic>N</jats:italic> <jats:sup>4</jats:sup> -acetylcytidine (ac <jats:sup>4</jats:sup> C) modification catalyzed by <jats:italic>N</jats:italic> -acetyltransferase 10 (NAT10), are unknown. In this study, we developed a low-input ac <jats:sup>4</jats:sup> C sequencing technology, ac <jats:sup>4</jats:sup> C LACE-seq, and mapped 8241 ac <jats:sup>4</jats:sup> C peaks at the whole-transcriptome level using 50 mouse oocytes at the germinal vesicle stage. Oocyte-specific <jats:italic>Nat10</jats:italic> knockout wiped out ac <jats:sup>4</jats:sup> C signals in oocytes and caused severe defects in meiotic maturation and female infertility. Mechanically, <jats:italic>Nat10</jats:italic> deletion led to a failure of ac <jats:sup>4</jats:sup> C deposition on mRNAs encoding key maternal factors, which regulate transcriptome stability and maternal-to-zygotic transition. <jats:italic>Nat10</jats:italic> -deleted oocytes showed decreased mRNA translation efficiency due to the direct inhibition of ac <jats:sup>4</jats:sup> C sites on specific transcripts during meiotic maturation. In summary, we developed a low-input, high-sensitivity mRNA ac <jats:sup>4</jats:sup> C profiling approach and highlighted the important physiological function of ac <jats:sup>4</jats:sup> C in the precise regulation of oocyte meiotic maturation by enhancing translation efficiency.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"20 1","pages":""},"PeriodicalIF":11.7000,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science Advances","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1126/sciadv.adp5163","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0

Abstract

The precise translational regulation of maternal messenger RNAs (mRNAs) drives mammalian oocyte maturation. However, the function and mechanism of posttranscriptional chemical modifications, especially the newly identified N 4 -acetylcytidine (ac 4 C) modification catalyzed by N -acetyltransferase 10 (NAT10), are unknown. In this study, we developed a low-input ac 4 C sequencing technology, ac 4 C LACE-seq, and mapped 8241 ac 4 C peaks at the whole-transcriptome level using 50 mouse oocytes at the germinal vesicle stage. Oocyte-specific Nat10 knockout wiped out ac 4 C signals in oocytes and caused severe defects in meiotic maturation and female infertility. Mechanically, Nat10 deletion led to a failure of ac 4 C deposition on mRNAs encoding key maternal factors, which regulate transcriptome stability and maternal-to-zygotic transition. Nat10 -deleted oocytes showed decreased mRNA translation efficiency due to the direct inhibition of ac 4 C sites on specific transcripts during meiotic maturation. In summary, we developed a low-input, high-sensitivity mRNA ac 4 C profiling approach and highlighted the important physiological function of ac 4 C in the precise regulation of oocyte meiotic maturation by enhancing translation efficiency.
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
求助全文
约1分钟内获得全文 去求助
来源期刊
Science Advances
Science Advances 综合性期刊-综合性期刊
CiteScore
21.40
自引率
1.50%
发文量
1937
审稿时长
29 weeks
期刊介绍: Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.
期刊最新文献
A galactose-tethered tetraphenylethene prodrug mediated apoptosis of senescent cells for osteoporosis treatment. General strategy for boosting the performance of speed-tunable rotary molecular motors with visible light. Immunogenic cryptic peptides dominate the antigenic landscape of ovarian cancer. Intratumoral antigen-presenting cell activation by a nanovesicle for the concurrent tertiary lymphoid structure de novo neogenesis. Accelerated internal tides in a warming climate.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1