Identification of Flavin Mononucleotide as a Cell-Active Artificial N -Methyladenosine RNA Demethylase.

N -Methyladenosine (m 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 A residues in mRNA. Herein, the first identification of a small-molecule modulator that functions as an artificial m A demethylase is reported. Flavin mononucleotide (FMN), the metabolite produced by riboflavin kinase, mediates substantial photochemical demethylation of m A residues of RNA in live cells. This study provides a new perspective to the understanding of demethylation of m 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.