Gao Zewei, Zha Xuan, Li Min, Xia Xueli, Wang Shengjun
Department of Laboratory Medicine，Jiangsu Province Engineering Research Center for Precise Diagnosis and Treatment of Inflammatory Diseases, The Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, China.
Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China.
Cell Biosci. 2024 Aug 27;14(1):108. doi: 10.1186/s13578-024-01286-6.
N6-methyladenosine (mA) is dynamically regulated by methyltransferases (termed "writers") and demethylases (referred to as "erasers"), facilitating a reversible modulation. Changes in mA 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 mA modulation has emerged as a promising therapeutic target across many diseases. mA 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 mA 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.
N6-甲基腺苷（mA）由甲基转移酶（称为“书写器”）和去甲基酶（称为“擦除器”）动态调控，实现可逆调节。mA水平的变化显著影响细胞功能，如RNA从细胞核输出、mRNA代谢、蛋白质合成和RNA剪接。它们与一系列病理状况密切相关。此外，mA调节失调已成为多种疾病中一个有前景的治疗靶点。mA在控制重要的下游分子和关键生物学途径中起关键作用，参与多种疾病的发病机制和进展。本综述概述了mA去甲基酶，详细阐述了FTO和ALKBH5的结构和功能特征。此外，我们探讨了它们在各种疾病中的不同作用，研究了调节其表达的因素，并讨论了抑制剂开发的进展。
