Functions and therapeutic applications of pseudouridylation

IF 81.3 1区 生物学 Q1 CELL BIOLOGY
Nan Luo, Qiang Huang, Meiling Zhang, Chengqi Yi
{"title":"Functions and therapeutic applications of pseudouridylation","authors":"Nan Luo, Qiang Huang, Meiling Zhang, Chengqi Yi","doi":"10.1038/s41580-025-00852-1","DOIUrl":null,"url":null,"abstract":"<p>The success of using pseudouridine (Ψ) and its methylation derivative in mRNA vaccines against SARS-CoV-2 has sparked a renewed interest in this RNA modification, known as the ‘fifth nucleotide’ of RNA. In this Review, we discuss the emerging functions of pseudouridylation in gene regulation, focusing on how pseudouridine in mRNA, tRNA and ribosomal RNA (rRNA) regulates translation. We also discuss the effects of pseudouridylation on RNA secondary structure, pre-mRNA splicing, and in vitro mRNA stability. In addition to nuclear-genome-encoded RNAs, pseudouridine is also present in mitochondria-encoded rRNA, mRNA and tRNA, where it has different distributions and functions compared with their nuclear counterparts. We then discuss the therapeutic potential of programmable pseudouridylation and mRNA vaccine optimization through pseudouridylation. Lastly, we briefly describe the latest quantitative pseudouridine detection methods. We posit that pseudouridine is a highly promising modification that merits further epitranscriptomics investigation and therapeutic application.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"39 1","pages":""},"PeriodicalIF":81.3000,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Reviews Molecular Cell Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1038/s41580-025-00852-1","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

The success of using pseudouridine (Ψ) and its methylation derivative in mRNA vaccines against SARS-CoV-2 has sparked a renewed interest in this RNA modification, known as the ‘fifth nucleotide’ of RNA. In this Review, we discuss the emerging functions of pseudouridylation in gene regulation, focusing on how pseudouridine in mRNA, tRNA and ribosomal RNA (rRNA) regulates translation. We also discuss the effects of pseudouridylation on RNA secondary structure, pre-mRNA splicing, and in vitro mRNA stability. In addition to nuclear-genome-encoded RNAs, pseudouridine is also present in mitochondria-encoded rRNA, mRNA and tRNA, where it has different distributions and functions compared with their nuclear counterparts. We then discuss the therapeutic potential of programmable pseudouridylation and mRNA vaccine optimization through pseudouridylation. Lastly, we briefly describe the latest quantitative pseudouridine detection methods. We posit that pseudouridine is a highly promising modification that merits further epitranscriptomics investigation and therapeutic application.

Abstract Image

假尿嘧啶化的功能和治疗应用
在针对SARS-CoV-2的mRNA疫苗中使用假尿嘧啶(Ψ)及其甲基化衍生物的成功引发了对这种被称为RNA的“第五核苷酸”的RNA修饰的新兴趣。在这篇综述中,我们讨论了假尿嘧啶化在基因调控中的新功能,重点讨论了mRNA、tRNA和核糖体RNA (rRNA)中的假尿嘧啶如何调节翻译。我们还讨论了假尿嘧啶化对RNA二级结构、mRNA前剪接和体外mRNA稳定性的影响。除了核基因组编码的rna外,假尿嘧啶也存在于线粒体编码的rRNA、mRNA和tRNA中,其分布和功能与核编码的rRNA、mRNA和tRNA不同。然后我们讨论了可编程假尿嘧啶化的治疗潜力和通过假尿嘧啶化优化mRNA疫苗。最后简要介绍了最新的伪尿嘧啶定量检测方法。我们认为假尿嘧啶是一种非常有前途的修饰物,值得进一步的表转录组学研究和治疗应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Nature Reviews Molecular Cell Biology
Nature Reviews Molecular Cell Biology 生物-细胞生物学
CiteScore
173.60
自引率
0.50%
发文量
118
审稿时长
6-12 weeks
期刊介绍: Nature Reviews Molecular Cell Biology is a prestigious journal that aims to be the primary source of reviews and commentaries for the scientific communities it serves. The journal strives to publish articles that are authoritative, accessible, and enriched with easily understandable figures, tables, and other display items. The goal is to provide an unparalleled service to authors, referees, and readers, and the journal works diligently to maximize the usefulness and impact of each article. Nature Reviews Molecular Cell Biology publishes a variety of article types, including Reviews, Perspectives, Comments, and Research Highlights, all of which are relevant to molecular and cell biologists. The journal's broad scope ensures that the articles it publishes reach the widest possible audience.
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信