Jin Ruoting, Zou Quan, Luo Ximei
Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu 611731, China.
Faculty of Applied Sciences, Macao Polytechnic University, Macau 999078, China.
Int J Mol Sci. 2025 Jul 12;26(14):6701. doi: 10.3390/ijms26146701.
N6-methyladenosine (m6A) represents the most common and thoroughly investigated RNA modification and exerts essential functions in regulating gene expression through influencing the RNA stability, the translation efficiency, alternative splicing, and nuclear export processes. The rapid development of high-throughput sequencing approaches, including miCLIP and MeRIP-seq, has profoundly transformed epitranscriptomics research. These techniques facilitate the detailed transcriptome-wide profiling of m6A modifications, shedding light on their crucial roles in diverse biological pathways. This review comprehensively examines the identification, mechanisms of regulation, and functional consequences of m6A modifications. It emphasizes their critical roles in physiological contexts, encompassing immune function, neuronal development, and the differentiation of stem cells. Additionally, the review discusses the contributions of m6A dysregulation to pathological conditions, including cancer, neurodegenerative diseases, and disorders of metabolism. We also discuss the development and application of machine-learning algorithms for m6A site prediction, emphasizing the integration of sequence-based, structural, and evolutionary conservation features to enhance the predictive accuracy. Furthermore, the potential of applying the findings from m6A research in precision medicine and drug development is examined. By synthesizing the current knowledge and emerging trends, this review aims to provide a comprehensive understanding of m6A biology and its translational potential, offering new perspectives for future research and therapeutic innovation.
N6-甲基腺苷(m6A)是最常见且研究最深入的RNA修饰,通过影响RNA稳定性、翻译效率、可变剪接和核输出过程,在调节基因表达中发挥重要作用。包括miCLIP和MeRIP-seq在内的高通量测序方法的迅速发展,深刻改变了表观转录组学研究。这些技术有助于对m6A修饰进行全转录组范围的详细分析,揭示其在多种生物途径中的关键作用。本综述全面探讨了m6A修饰的鉴定、调控机制和功能后果。强调了它们在生理环境中的关键作用,包括免疫功能、神经元发育和干细胞分化。此外,综述还讨论了m6A失调对病理状况的影响,包括癌症、神经退行性疾病和代谢紊乱。我们还讨论了用于m6A位点预测的机器学习算法的开发和应用,强调整合基于序列、结构和进化保守性的特征以提高预测准确性。此外,还探讨了将m6A研究结果应用于精准医学和药物开发的潜力。通过综合当前知识和新出现的趋势,本综述旨在全面了解m6A生物学及其转化潜力,为未来研究和治疗创新提供新的视角。