Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China.
Institute of Integrative Medicine, Fudan University, Shanghai, China.
Cancer Gene Ther. 2024 Oct;31(10):1439-1453. doi: 10.1038/s41417-024-00789-1. Epub 2024 Jun 5.
Post-transcriptional RNA modification is an emerging epigenetic control mechanism in cells that is important in many different cellular and organismal processes. N6-methyladenosine (mA) is one of the most prevalent, prolific, and ubiquitous internal transcriptional alterations in eukaryotic mRNAs, making it an important topic in the field of Epigenetics. mA methylation acts as a dynamical regulatory process that regulates the activity of genes and participates in multiple physiological processes, by supporting multiple aspects of essential mRNA metabolic processes, including pre-mRNA splicing, nuclear export, translation, miRNA synthesis, and stability. Extensive research has linked aberrations in mA modification and mA-associated proteins to a wide range of human diseases. However, the impact of mA on mRNA metabolism and its pathological connection between mA and other non-communicable diseases, including cardiovascular disease, neurodegenerative disorders, liver diseases, and cancer remains in fragmentation. Here, we review the existing understanding of the overall role of mechanisms by which mA exerts its activities and address new discoveries that highlight mA's diverse involvement in gene expression regulation. We discuss mA deposition on mRNA and its consequences on degradation, translation, and transcription, as well as mA methylation of non-coding chromosomal-associated RNA species. This study could give new information about the molecular process, early detection, tailored treatment, and predictive evaluation of human non-communicable diseases like cancer. We also explore more about new data that suggests targeting mA regulators in diseases may have therapeutic advantages.
RNA 转录后修饰是细胞中一种新兴的表观遗传调控机制，在许多不同的细胞和生物过程中都很重要。N6-甲基腺苷（mA）是真核 mRNA 中最普遍、最多产和最普遍的内部转录改变之一，因此它是表观遗传学领域的一个重要课题。mA 甲基化作为一种动态调节过程，通过支持 mRNA 代谢过程的多个方面，包括前体 mRNA 剪接、核输出、翻译、miRNA 合成和稳定性，调节基因的活性并参与多种生理过程。大量研究将 mA 修饰和 mA 相关蛋白的异常与广泛的人类疾病联系起来。然而，mA 对 mRNA 代谢的影响及其与心血管疾病、神经退行性疾病、肝脏疾病和癌症等其他非传染性疾病之间的病理联系仍然存在碎片化。在这里，我们回顾了对 mA 发挥其活性的机制的整体作用的现有理解，并探讨了强调 mA 参与基因表达调控的多样性的新发现。我们讨论了 mA 在 mRNA 上的沉积及其对降解、翻译和转录的影响，以及非编码染色体相关 RNA 物种的 mA 甲基化。这项研究可以为癌症等人类非传染性疾病的分子过程、早期检测、针对性治疗和预测评估提供新信息。我们还探讨了更多新数据，表明针对疾病中的 mA 调节剂可能具有治疗优势。
