Identification of Flavin Mononucleotide as a Cell-Active Artificial N6-Methyladenosine RNA Demethylase
Identification of Flavin Mononucleotide as a Cell-Active Artificial N6-Methyladenosine RNA Demethylase
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黄素单核苷酸作为细胞活性人工 N6-甲基腺苷 RNA 脱甲基酶的鉴定
DOI：
10.1002/anie.201900901
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发表时间：
2019-04-01
影响因子：
16.6
通讯作者：
Cheng, Liang
中科院分区：
文献类型：
--
作者：
Xie, Li-Jun;Yang, Xiao-Ti;Cheng, Liang
N-6-甲基腺苷（m（6）A）是真核生物RNA中一种常见的高度动态修饰，影响多种细胞途径。天然双加氧酶如FTO和ALKBH 5是使mRNA中的m（6）A残基脱甲基化的酶。本文报道了作为人工m（6）A脱甲基酶的小分子调节剂的首次鉴定。核黄素激酶产生的代谢产物黄素单核苷酸（FMN）介导活细胞中RNA的m（6）A残基的大量光化学去甲基化。这项研究为理解mRNA中m（6）A残基的去甲基化提供了一个新的视角，并为开发功能强大的小分子RNA去甲基化酶和用于RNA生物学的新探针提供了线索。
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.