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.

IF 3.4 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY NAR cancer Pub Date : 2025-01-28 eCollection Date: 2025-03-01 DOI:10.1093/narcan/zcaf001

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

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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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