{"title":"Dynamic Regulation of 5-Formylcytidine on tRNA.","authors":"Xuemeng Sun, Ralph E Kleiner","doi":"10.1021/acschembio.4c00866","DOIUrl":null,"url":null,"abstract":"<p><p>Post-transcriptional modifications on RNA play an important role in biological processes, but we lack an understanding of the molecular mechanisms underlying the function of many modifications. Here we characterize the distribution and dynamic regulation of 5-formylcytidine (f<sup>5</sup>C), a modification primarily found on tRNAs, across different cell lines, mouse tissues, and in response to environmental stress. We identify perturbation in bulk f<sup>5</sup>C levels using nucleoside LC-MS and quantify individual modification stoichiometry at the wobble base of mt-tRNA-Met and tRNA-Leu-CAA using nucleotide resolution f<sup>5</sup>C sequencing technology. Our studies show that f<sup>5</sup>C modifications on tRNAs are dynamic, and responsive to fluctuations in cellular iron levels and O<sub>2</sub> concentration. Further, we show using a translation reporter assay that decoding of Leu UUA codons is impaired in cells lacking f<sup>5</sup>C, implicating f<sup>5</sup>C(m)34 on tRNA-Leu-CAA in wobble decoding. Together, our work illuminates dynamic epitranscriptomic mechanisms regulating protein translation in response to environment.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Chemical Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1021/acschembio.4c00866","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Post-transcriptional modifications on RNA play an important role in biological processes, but we lack an understanding of the molecular mechanisms underlying the function of many modifications. Here we characterize the distribution and dynamic regulation of 5-formylcytidine (f5C), a modification primarily found on tRNAs, across different cell lines, mouse tissues, and in response to environmental stress. We identify perturbation in bulk f5C levels using nucleoside LC-MS and quantify individual modification stoichiometry at the wobble base of mt-tRNA-Met and tRNA-Leu-CAA using nucleotide resolution f5C sequencing technology. Our studies show that f5C modifications on tRNAs are dynamic, and responsive to fluctuations in cellular iron levels and O2 concentration. Further, we show using a translation reporter assay that decoding of Leu UUA codons is impaired in cells lacking f5C, implicating f5C(m)34 on tRNA-Leu-CAA in wobble decoding. Together, our work illuminates dynamic epitranscriptomic mechanisms regulating protein translation in response to environment.
期刊介绍：
ACS Chemical Biology provides an international forum for the rapid communication of research that broadly embraces the interface between chemistry and biology.
The journal also serves as a forum to facilitate the communication between biologists and chemists that will translate into new research opportunities and discoveries. Results will be published in which molecular reasoning has been used to probe questions through in vitro investigations, cell biological methods, or organismic studies.
We welcome mechanistic studies on proteins, nucleic acids, sugars, lipids, and nonbiological polymers. The journal serves a large scientific community, exploring cellular function from both chemical and biological perspectives. It is understood that submitted work is based upon original results and has not been published previously.
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