Insights into the m⁶A demethylases FTO and ALKBH5 : structural, biological function, and inhibitor development.

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell and Bioscience Pub Date : 2024-08-27 DOI:10.1186/s13578-024-01286-6

Zewei Gao, Xuan Zha, Min Li, Xueli Xia, Shengjun Wang

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引用次数: 0

Abstract

N6-methyladenosine (m⁶A) is dynamically regulated by methyltransferases (termed "writers") and demethylases (referred to as "erasers"), facilitating a reversible modulation. Changes in m⁶A levels significantly influence cellular functions, such as RNA export from the nucleus, mRNA metabolism, protein synthesis, and RNA splicing. They are intricately associated with a spectrum of pathologies. Moreover, dysregulation of m⁶A modulation has emerged as a promising therapeutic target across many diseases. m⁶A plays a pivotal role in controlling vital downstream molecules and critical biological pathways, contributing to the pathogenesis and evolution of numerous conditions. This review provides an overview of m⁶A demethylases, explicitly detailing the structural and functional characteristics of FTO and ALKBH5. Additionally, we explore their distinct involvement in various diseases, examine factors regulating their expression, and discuss the progress in inhibitor development.

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洞察 m6A 去甲基化酶 FTO 和 ALKBH5：结构、生物功能和抑制剂开发。

N6-甲基腺苷（m6A）受甲基转移酶（称为 "书写者"）和去甲基化酶（称为 "擦除者"）的动态调节，从而实现可逆调节。m6A 水平的变化对细胞功能有重大影响，如从细胞核输出 RNA、mRNA 代谢、蛋白质合成和 RNA 剪接。它们与一系列病理现象密切相关。此外，m6A 调控失调已成为许多疾病的治疗靶点。m6A 在控制重要下游分子和关键生物通路方面发挥着关键作用，导致了许多疾病的发病和演变。本综述概述了 m6A 去甲基化酶，明确详述了 FTO 和 ALKBH5 的结构和功能特点。此外，我们还探讨了它们在各种疾病中的不同参与方式，研究了调控它们表达的因素，并讨论了抑制剂开发方面的进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell and Bioscience BIOCHEMISTRY & MOLECULAR BIOLOGY-

CiteScore

10.70

自引率

0.00%

发文量

187

审稿时长

>12 weeks

期刊介绍： Cell and Bioscience, the official journal of the Society of Chinese Bioscientists in America, is an open access, peer-reviewed journal that encompasses all areas of life science research.