{"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.
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.
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