背景 N6-甲基腺苷 (m6A) 是真核生物中最常见的内部 mRNA 修饰，由 m6A 甲基转移酶添加，由 m6A 去甲基酶去除，并由 m6A 结合蛋白识别。这种修饰显着影响 RNA 代谢的各个方面，并在细胞和生理过程中发挥关键作用。主体前 mRNA 选择性剪接是一种从多外显子基因产生多个剪接亚型的过程，对哺乳动物的蛋白质多样性做出了重大贡献。此外，已经确定 m6A 修饰和选择性剪接之间存在串扰，其中 m6A 对前 mRNA 的修饰发挥调节控制作用。 m6A 修饰通过招募调节选择性剪接的特定 RNA 结合蛋白 (RBP) 或直接影响 RBP 与其靶 RNA 之间的相互作用来调节选择性剪接模式。相反，选择性剪接会影响 m6A 修饰在 mRNA 上的沉积或识别。 m6A 修饰的整合扩大了癌症治疗策略的范围，而选择性剪接为 m6A 甲基化在癌症发生和进展中的机制作用提供了新的见解。结论 本综述旨在强调 m6A 修饰机制选择性剪接的生物学功能及其在肿瘤发生中的意义。此外，我们讨论了理解肿瘤治疗中 m6A 依赖性选择性剪接的临床意义。© 2023 作者。约翰·威利出版的《临床与转化医学》

Background N6-methyladenosine (m6A), the most prevalent internal mRNA modification in eukaryotes, is added by m6A methyltransferases, removed by m6A demethylases and recognised by m6A-binding proteins. This modification significantly influences carious facets of RNA metabolism and plays a pivotal role in cellular and physiological processes. Main body Pre-mRNA alternative splicing, a process that generates multiple splice isoforms from multi-exon genes, contributes significantly to the protein diversity in mammals. Moreover, the presence of crosstalk between m6A modification and alternative splicing, with m6A modifications on pre-mRNAs exerting regulatory control, has been established. The m6A modification modulates alternative splicing patterns by recruiting specific RNA-binding proteins (RBPs) that regulate alternative splicing or by directly influencing the interaction between RBPs and their target RNAs. Conversely, alternative splicing can impact the deposition or recognition of m6A modification on mRNAs. The integration of m6A modifications has expanded the scope of therapeutic strategies for cancer treatment, while alternative splicing offers novel insights into the mechanistic role of m6A methylation in cancer initiation and progression. Conclusion This review aims to highlight the biological functions of alternative splicing of m6A modification machinery and its implications in tumourigenesis. Furthermore, we discuss the clinical relevance of understanding m6A-dependent alternative splicing in tumour therapies.© 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.