N6-甲基腺苷 (m6A) 是真核 RNA 中最丰富的内源修饰。它在包括癌症在内的各种生物过程和疾病中发挥着重要作用。越来越多的研究表明，m6A 的沉积以上下文相关的方式受到特异性调控。在这里，我们回顾了决定 m6A 沿 RNA 的拓扑结构和细胞类型特异性 m6A 甲基化组的多种机制。外显子连接复合物 (EJC) 以及组蛋白修饰在确定 m6A 沿新生 RNA 的拓扑分布方面发挥着重要作用；而转录因子RNA结合蛋白通常以细胞类型特异性的方式结合特定的DNA和RNA，在很大程度上解释了细胞类型特异性的m6A甲基化组。由于 m6A 编写者和读者缺乏特异​​性，针对癌症治疗的核心 m6A 机制仍然存在挑战。因此，了解癌症中 m6A 修饰特异性的机制对于未来通过 m6A 干预进行癌症治疗非常重要。版权所有 © 2024。由 Elsevier Inc. 出版。

N6-methyladenosine (m6A) is the most abundant endogenous modification in eukaryotic RNAs. It plays important roles in various biological processes and diseases, including cancers. More and more studies have revealed that the deposition of m6A is specifically regulated in a context-dependent manner. Here, we review the diverse mechanisms that determine the topology of m6A along RNAs and the cell type-specific m6A methylomes. The Exon Junction Complex (EJC) as well as histone modifications play important roles in determining the topological distribution of m6A along nascent RNAs; while the transcription factors, RNA binding proteins, which usually bind specific DNAs and RNAs in a cell type-specific manner, largely account for the cell type-specific m6A methylomes. Due to the lack of specificity of m6A writers and readers, there are still challenges to target the core m6A machinery for cancer therapies. Therefore, understanding the mechanisms underlying the specificity of m6A modifications in cancers would be important for future cancer therapies through m6A intervention.Copyright © 2024. Published by Elsevier Inc.