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

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.