Specific modulation of 28S_Um2402 rRNA 2'-O-ribose methylation as a novel epitranscriptomic marker of ZEB1-induced epithelial-mesenchymal transition in different mammary cell contexts.
{"title":"Specific modulation of 28S_Um2402 rRNA 2'-<i>O</i>-ribose methylation as a novel epitranscriptomic marker of ZEB1-induced epithelial-mesenchymal transition in different mammary cell contexts.","authors":"Chloé Morin, Hermes Paraqindes, Flora Nguyen Van Long, Caroline Isaac, Emilie Thomas, Dennis Pedri, Carlos Ariel Pulido-Vicuna, Anne-Pierre Morel, Virginie Marchand, Yuri Motorin, Marjorie Carrere, Jessie Auclair, Valéry Attignon, Roxane M Pommier, Emmanuelle Ruiz, Fleur Bourdelais, Frédéric Catez, Sébastien Durand, Anthony Ferrari, Alain Viari, Jean-Christophe Marine, Alain Puisieux, Jean-Jacques Diaz, Caroline Moyret-Lalle, Virginie Marcel","doi":"10.1093/narcan/zcaf001","DOIUrl":null,"url":null,"abstract":"<p><p>The epithelial-mesenchymal transition (EMT) is a dynamic transdifferentiation of epithelial cells into mesenchymal cells. EMT programs exhibit great diversity, based primarily on the distinct impact of molecular activities of the EMT transcription factors. Using a panel of cancer cell lines and a series of 71 triple-negative primary breast tumors, we report that the EMT transcription factor ZEB1 modulates site-specific chemical modifications of ribosomal RNA (rRNA). Overexpression of ZEB1 and ZEB2, but not TWIST1, decreased the level of 2'-<i>O</i>-ribose methylation (2'Ome) of 28S rRNA at position Um2402. ZEB1 overexpression specifically reduced the expression of the corresponding C/D box small nucleolar RNAs (snoRNAs) SNORD143/144, which guide the rRNA 2'Ome complex at the 28S_Um2402 site. During ZEB1-induced EMT induction/reversion, the levels of both 2'Ome at 28S_Um2402 and SNORD143/144 were dynamically comodulated. Taken together, these data demonstrate that 2'Ome rRNA epitranscriptomics is a novel marker of ZEB1-induced EMT.</p>","PeriodicalId":94149,"journal":{"name":"NAR cancer","volume":"7 1","pages":"zcaf001"},"PeriodicalIF":3.4000,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773364/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"NAR cancer","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/narcan/zcaf001","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
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Abstract
The epithelial-mesenchymal transition (EMT) is a dynamic transdifferentiation of epithelial cells into mesenchymal cells. EMT programs exhibit great diversity, based primarily on the distinct impact of molecular activities of the EMT transcription factors. Using a panel of cancer cell lines and a series of 71 triple-negative primary breast tumors, we report that the EMT transcription factor ZEB1 modulates site-specific chemical modifications of ribosomal RNA (rRNA). Overexpression of ZEB1 and ZEB2, but not TWIST1, decreased the level of 2'-O-ribose methylation (2'Ome) of 28S rRNA at position Um2402. ZEB1 overexpression specifically reduced the expression of the corresponding C/D box small nucleolar RNAs (snoRNAs) SNORD143/144, which guide the rRNA 2'Ome complex at the 28S_Um2402 site. During ZEB1-induced EMT induction/reversion, the levels of both 2'Ome at 28S_Um2402 and SNORD143/144 were dynamically comodulated. Taken together, these data demonstrate that 2'Ome rRNA epitranscriptomics is a novel marker of ZEB1-induced EMT.
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