鉴定黄素单核苷酸为一种细胞活性的人工 N6-甲基腺苷 RNA 去甲基酶。

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

机构信息

Beijing National Laboratory for Molecular Sciences (BNLMS), CAS Key Laboratory of Molecular Recognition and Function, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.

University of Chinese Academy of Sciences, Beijing, 100049, China.

出版信息

Angew Chem Int Ed Engl. 2019 Apr 1;58(15):5028-5032. doi: 10.1002/anie.201900901. Epub 2019 Mar 12.

DOI:10.1002/anie.201900901

PMID:30756480

Abstract

N -Methyladenosine (m 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 A residues in mRNA. Herein, the first identification of a small-molecule modulator that functions as an artificial m A demethylase is reported. Flavin mononucleotide (FMN), the metabolite produced by riboflavin kinase, mediates substantial photochemical demethylation of m A residues of RNA in live cells. This study provides a new perspective to the understanding of demethylation of m 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.

摘要

N6-甲基腺苷（m6A）是真核 RNA 中一种常见且高度动态的修饰，可影响多种细胞通路。天然的双氧酶如 FTO 和 ALKBH5 是可以使 mRNA 中的 m6A 去甲基化的酶。本文首次报道了一种小分子调节剂，其可作为人工 m6A 去甲基酶发挥作用。黄素单核苷酸（FMN）是核黄素激酶产生的代谢产物，可介导活细胞中 RNA 的 m6A 残基的显著光化学去甲基化。本研究为理解 mRNA 中 m6A 残基的去甲基化提供了新视角，并为开发作为 RNA 去甲基酶的有效小分子以及用于 RNA 生物学的新探针提供了思路。