Malvi Parmanand, Ball Patrick, Gupta Romi, Wajapeyee Narendra
Department of Biochemistry and Molecular Genetics, The University of Alabama at Birmingham, Birmingham, Alabama, USA.
O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.
J Immunother Cancer. 2025 Sep 3;13(9):e012744. doi: 10.1136/jitc-2025-012744.
RNA molecules are subject to extensive post-transcriptional modifications that fine-tune their stability, localization, and function. Among the more than 100 known RNA modifications, N6-methyladenosine (mA) is the most abundant internal mark on eukaryotic messenger RNAs. This dynamic modification is installed by methyltransferases ("writers"), removed by demethylases ("erasers"), and interpreted by RNA-binding proteins ("readers") to modulate gene expression. In this review, we examine the mechanisms governing mA deposition and its broad impact on mRNA fate. We then focus on the emerging roles of mA in shaping antitumor immune responses and discuss how targeting mA-regulated pathways can enhance the efficacy of existing immunotherapies. Finally, we highlight recent advances and ongoing challenges in the development of drugs that target key regulators of mA RNA modifications.
RNA分子会经历广泛的转录后修饰，这些修饰可微调其稳定性、定位和功能。在100多种已知的RNA修饰中，N6-甲基腺苷（mA）是真核生物信使RNA上最丰富的内部标记。这种动态修饰由甲基转移酶（“书写者”）安装，由去甲基化酶（“擦除者”）去除，并由RNA结合蛋白（“阅读者”）解读，以调节基因表达。在本综述中，我们研究了控制mA沉积的机制及其对mRNA命运的广泛影响。然后，我们重点关注mA在塑造抗肿瘤免疫反应中的新作用，并讨论靶向mA调节途径如何提高现有免疫疗法的疗效。最后，我们强调了靶向mA RNA修饰关键调节因子的药物开发的最新进展和持续挑战。
