HOTAIR requires epitranscriptomic modification to exert its pivotal epigenetic role in Epithelial to Mesenchymal Transition.

ABSTRACT: While m6A epitranscriptomic modification has been shown to impact several mRNAs maturation, stability/degradation, nuclear/cytoplasm export and translation regulation, its impact on lncRNAs activity is yet largely uncharacterized. Here, we show that the silencing of the m6A writer METTL3 inhibits Epithelial to Mesenchymal Transition (EMT), morphological, migratory and invasive features of TGFβ-treated epithelial cells as well as of tumor cells. Building on previous evidence pinpointing the lncHOTAIR as a mandatory element for epithelial genes' repression triggering EMT, here we uncover a dominant role of an epitranscriptomic modification on the epigenetic function of this lncRNA. Mechanistically, HOTAIR is m6A-modified on the interaction domains with both the master transcriptional factor

SUBMITTER: Garbo S 

PROVIDER: S-EPMC12552435 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature