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

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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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