{"title":"Expanding Epitranscriptomics to Non-Enzymatic RNA Modifications.","authors":"Kaila Nishikawa, Yael David, Anna Knörlein","doi":"10.1016/j.trechm.2025.08.005","DOIUrl":null,"url":null,"abstract":"<p><p>Cells regulate responses to external stimuli and control cell fate through reversible modifications on proteins, DNA, and RNA typically introduced by enzymes. Next to these well-known enzymatically installed modifications, covalent modifications can also occur on these same biomolecules through spontaneous reaction with small molecules taken up from external sources or generated endogenously, e.g. byproducts of metabolic processes. These so-called non-enzymatic covalent modifications (NECMs) have been mainly studied on proteins and DNA, yet their biological role on RNA remains mostly underexplored. This review surveys identified and predicted RNA NECMs, explores their impact on RNA structure, stability, and function, and examines their potential link to diseases. Finally, we discuss regulation mechanisms of non-enzymatically modified RNAs and their potential significance on cellular dynamics.</p>","PeriodicalId":48544,"journal":{"name":"Trends in Chemistry","volume":" ","pages":""},"PeriodicalIF":13.6000,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524911/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Trends in Chemistry","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1016/j.trechm.2025.08.005","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
Cells regulate responses to external stimuli and control cell fate through reversible modifications on proteins, DNA, and RNA typically introduced by enzymes. Next to these well-known enzymatically installed modifications, covalent modifications can also occur on these same biomolecules through spontaneous reaction with small molecules taken up from external sources or generated endogenously, e.g. byproducts of metabolic processes. These so-called non-enzymatic covalent modifications (NECMs) have been mainly studied on proteins and DNA, yet their biological role on RNA remains mostly underexplored. This review surveys identified and predicted RNA NECMs, explores their impact on RNA structure, stability, and function, and examines their potential link to diseases. Finally, we discuss regulation mechanisms of non-enzymatically modified RNAs and their potential significance on cellular dynamics.
期刊介绍：
Trends in Chemistry serves as a new global platform for discussing significant and transformative concepts across all areas of chemistry. It recognizes that breakthroughs in chemistry hold the key to addressing major global challenges. The journal offers readable, multidisciplinary articles, including reviews, opinions, and short pieces, designed to keep both students and leading scientists updated on pressing issues in the field.
Covering analytical, inorganic, organic, physical, and theoretical chemistry, the journal highlights major themes such as biochemistry, catalysis, environmental chemistry, materials, medicine, polymers, and supramolecular chemistry. It also welcomes articles on chemical education, health and safety, policy and public relations, and ethics and law.
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