Identification of Flavin Mononucleotide as a Cell‐Active Artificial N 6‐Methyladenosine RNA Demethylase

作者：Li‐Jun Xie; Xiao‐Ti Yang; Rui‐Li Wang; Hou‐Ping Cheng; Zhi‐Yan Li; Prof. Dr. Li Liu; Prof. Dr. Lanqun Mao; Prof. Dr. Ming Wang; Prof. Dr. Liang Cheng

来源：Angewandte Chemie, 2019, 131(15): 5082-5086.

DOI：10.1002/ange.201900901

• Artifizielle Enzyme
• Flavinmononukleotid
• RNA-Demethylase
• RNA-Demethylierung

N \u003csup\u003e6\u003c/sup\u003e‐Methyladenosine (m\u003csup\u003e6\u003c/sup\u003eA) 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\u003csup\u003e6\u003c/sup\u003eA residues in mRNA. Herein, the first identification of a small‐molecule modulator that functions as an artificial m\u003csup\u003e6\u003c/sup\u003eA demethylase is reported. Flavin mononucleotide (FMN), the metabolite produced by riboflavin kinase, mediates substantial photochemical demethylation of m\u003csup\u003e6\u003c/sup\u003eA residues of RNA in live cells. This study provides a new perspective to the understanding of demethylation of m\u003csup\u003e6\u003c/sup\u003eA residues in mRNA and sheds light on the development of powerful small molecules as RNA demethylases and new probes for use in RNA biology.

• 单位
  中国科学院