Systemic control of HNF1B-driven redox homeostasis by N6-adenosine methylation.

ABSTRACT: Transcription factors are key regulators of gene expression and play essential roles in various diseases, yet their lack of small-molecule binding pockets makes them difficult to target with drugs. Internal RNA modifications, such as N6-methyladenosine, are widespread in mammalian cells, but how m6A-encoded epitranscriptomic information influences transcription factor activity and cellular function remains incompletely understood. Here, we demonstrate that m6A methylation directly regulates HNF1B and is essential for maintaining redox homeostasis in cancer cells. The METTL3/METTL14 methyltransferase complex deposits m6A marks within the 3'-untranslated regions of HNF1B messenger RNA (mRNA), stabilizing its expression and function. Genetic or chemical inhibition of METTL3-mediated m6A modif

SUBMITTER: Park M 

PROVIDER: S-EPMC12774655 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature