化学所分子识别与功能实验室

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

Date:2019-03-20 Enlarge Narrow

Li-Jun Xie , Xiao-Ti Yang , Rui-Li Wang, Hou-Ping Cheng, Zhi-Yan Li, Li Liu, Lanqun Mao, Ming Wang,* and Liang Cheng*

  N6‐Methyladenosine (m6A) 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 m6A residues in mRNA. Herein, the first identification of a small‐molecule modulator that functions as an artificial m6A demethylase is reported. Flavin mononucleotide (FMN), the metabolite produced by riboflavin kinase, mediates substantial photochemical demethylation of m6A residues of RNA in live cells. This study provides a new perspective to the understanding of demethylation of m6A residues in mRNA and sheds light on the development of powerful small molecules as RNA demethylases and new probes for use in RNA biology.

This work has been published in Angew. Chem. Int. Ed. DOI: 10.1002/anie.201900901.