Li Na, Wei Xiang, Dai Jian, Yang Jinfeng, Xiong Sizheng
Division of Cardiothoracic and Vascular Surgery, Sino-Swiss Heart-Lung Transplantation Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Critical Care Medicine, Wuhan Wuchang Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei, China.
Mol Cell Biochem. 2025 Jan 24. doi: 10.1007/s11010-025-05208-z.
N6-methyladenosine (mA) methylation is the most prevalent and abundant internal modification of mRNAs and is catalyzed by the methyltransferase complex. Methyltransferase-like 3 (METTL3), the best-known mA methyltransferase, has been confirmed to function as a multifunctional regulator in the reversible epitranscriptome modulation of mA modification according to follow-up studies. Accumulating evidence in recent years has shown that METTL3 can regulate a variety of functional genes, that aberrant expression of METTL3 is usually associated with many pathological conditions, and that its expression regulatory mechanism is related mainly to its methyltransferase activity or mRNA posttranslational modification. In this review, we discuss the regulatory functions of METTL3 in various diseases, including metabolic diseases, cardiovascular diseases, and cancer. We focus mainly on recent progress in identifying the downstream target genes of METTL3 and its underlying molecular mechanisms and regulators in the above systems. Studies have revealed that the use of METTL3 as a therapeutic target and a new diagnostic biomarker has broad prospects. We hope that this review can serve as a reference for further studies.
N6-甲基腺苷（m6A）甲基化是mRNA中最普遍且丰富的内部修饰，由甲基转移酶复合物催化。类甲基转移酶3（METTL3）是最著名的m6A甲基转移酶，后续研究证实其在m6A修饰的可逆表观转录组调控中作为多功能调节因子发挥作用。近年来越来越多的证据表明，METTL3可调控多种功能基因，METTL3的异常表达通常与多种病理状况相关，其表达调控机制主要与其甲基转移酶活性或mRNA的翻译后修饰有关。在本综述中，我们讨论了METTL3在各种疾病中的调控功能，包括代谢性疾病、心血管疾病和癌症。我们主要关注在确定METTL3的下游靶基因及其在上述系统中的潜在分子机制和调节因子方面的最新进展。研究表明，将METTL3用作治疗靶点和新型诊断生物标志物具有广阔前景。我们希望本综述能为进一步研究提供参考。
