State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.
Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
Nat Rev Mol Cell Biol. 2023 Oct;24(10):714-731. doi: 10.1038/s41580-023-00622-x. Epub 2023 Jun 27.
Nucleobase modifications are prevalent in eukaryotic mRNA and their discovery has resulted in the emergence of epitranscriptomics as a research field. The most abundant internal (non-cap) mRNA modification is N-methyladenosine (mA), the study of which has revolutionized our understanding of post-transcriptional gene regulation. In addition, numerous other mRNA modifications are gaining great attention because of their major roles in RNA metabolism, immunity, development and disease. In this Review, we focus on the regulation and function of non-mA modifications in eukaryotic mRNA, including pseudouridine (Ψ), N,2'-O-dimethyladenosine (mAm), N-methyladenosine (mA), inosine, 5-methylcytidine (mC), N-acetylcytidine (acC), 2'-O-methylated nucleotide (Nm) and internal N-methylguanosine (mG). We highlight their regulation, distribution, stoichiometry and known roles in mRNA metabolism, such as mRNA stability, translation, splicing and export. We also discuss their biological consequences in physiological and pathological processes. In addition, we cover research techniques to further study the non-mA mRNA modifications and discuss their potential future applications.
核苷碱基修饰在真核 mRNA 中普遍存在，其发现促成了表观转录组学作为一个研究领域的出现。最丰富的内部（非帽）mRNA 修饰是 N6-甲基腺苷（m6A），对其的研究彻底改变了我们对转录后基因调控的理解。此外，由于其他许多 mRNA 修饰在 RNA 代谢、免疫、发育和疾病中发挥着重要作用，因此它们也受到了极大的关注。在这篇综述中，我们重点关注真核 mRNA 中非 m6A 修饰的调控和功能，包括假尿嘧啶（Ψ）、N2'-O-二甲基腺苷（mAm）、N6-甲基腺苷（m6A）、肌苷、5-甲基胞嘧啶（mC）、N-乙酰胞嘧啶（acC）、2'-O-甲基化核苷酸（Nm）和内部 N6-甲基鸟苷（m6G）。我们强调了它们在 mRNA 代谢中的调控、分布、化学计量和已知作用，如 mRNA 稳定性、翻译、剪接和输出。我们还讨论了它们在生理和病理过程中的生物学后果。此外，我们还介绍了用于进一步研究非 m6A mRNA 修饰的研究技术，并讨论了它们的潜在未来应用。
