Identification of Flavin Mononucleotide as a Cell‐Active Artificial N6‐Methyladenosine RNA Demethylase

Abstract N 6 ‐Methyladenosine (m 6 A) represents a common and highly dynamic modification in eukaryotic RNA that affects various cellular pathways. Natural dioxygenases such as FTO and ALKBH5 are enzymes that demethylate m 6 A residues in mRNA. Herein, the first identification of a small‐molecule modulator that functions as an artificial m 6 A demethylase is reported. Flavin mononucleotide (FMN), the metabolite produced by riboflavin kinase, mediates substantial photochemical demethylation of m 6 A residues of RNA in live cells. This study provides a new perspective to the understanding of demethylation of m 6 A residues in mRNA and sheds light on the development of powerful small molecules as RNA demethylases and new probes for use in RNA biology.