Fang Miaochun, Ye Liwen, Zhu Yue, Huang Linying, Xu Shun
Guangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, Institute of Aging Research, School of Medical Technology, Guangdong Medical University, Songshan Lake, Dongguan 523808, China.
Biomolecules. 2025 Jan 21;15(2):157. doi: 10.3390/biom15020157.
N6-methyladenosine (m6A) is the most abundant, dynamically reversible, and evolutionarily conserved internal chemical modification in eukaryotic RNA. It is emerging as critical for regulating gene expression at the post-transcriptional level by affecting RNA metabolism through, for example, pre-mRNA processing, mRNA decay, and translation. ALKBH5 has recently been identified as an endogenous m6A demethylase implicated in a multitude of biological processes. This review provides an overview of the structural and functional characteristics of ALKBH5 and the involvement of ALKBH5 in diverse human diseases, including metabolic, immune, reproductive, and nervous system disorders, as well as the development of inhibitors. In summation, this review highlights the current understanding of the structure, functions, and detailed mechanisms of ALKBH5 in various physiological and pathological processes and provides valuable insights for clinical applications and foundational research within related fields.
N6-甲基腺苷（m6A）是真核生物RNA中最丰富、动态可逆且进化保守的内部化学修饰。它通过影响RNA代谢，如前体mRNA加工、mRNA衰变和翻译等，在转录后水平调控基因表达方面正崭露头角。最近，ALKBH5被鉴定为一种内源性m6A去甲基化酶，参与众多生物学过程。本文综述了ALKBH5的结构和功能特性，以及ALKBH5在多种人类疾病中的作用，包括代谢、免疫、生殖和神经系统疾病，还介绍了其抑制剂的研发情况。总之，本文突出了当前对ALKBH5在各种生理和病理过程中的结构、功能及详细机制的理解，并为相关领域的临床应用和基础研究提供了有价值的见解。
