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Identification of Flavin Mononucleotide as a Cell‐Active Artificial N 6 ‐Methyladenosine RNA Demethylase
Author(s) -
Xie LiJun,
Yang XiaoTi,
Wang RuiLi,
Cheng HouPing,
Li ZhiYan,
Liu Li,
Mao Lanqun,
Wang Ming,
Cheng Liang
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201900901
Subject(s) - demethylase , flavin mononucleotide , rna , biochemistry , demethylation , n6 methyladenosine , chemistry , small molecule , flavin group , enzyme , flavin adenine dinucleotide , biology , methyltransferase , cofactor , epigenetics , methylation , gene expression , gene , dna methylation
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.