Characterization of human m3C tRNA methyltransferases

The three human 3-methyl-cytosine (m³C) tRNA methyltransferases have been implicated in various cancers and diseases. Each methyltransferase modifies a distinct subset of tRNAs, yet the molecular mechanisms underlying their substrate selection remain poorly understood, posing a challenge for the targeted design of therapeutic strategies. Prior to this, we presented a high-resolution cryo-EM structure of METTL6 and revealed how it achieves substrate-specificity for serine tRNAs. We are now proceeding to analyze the substrate recognition mechanisms in the related m3C tRNA methyltransferases METTL2 and METTL8.

三类人类3-甲基胞嘧啶（3-methyl-cytosine, m³C）tRNA甲基转移酶已被证实与多种癌症及疾病相关。每一种甲基转移酶均可修饰特定子集的tRNA，但其底物选择背后的分子机制仍不甚明晰，这为靶向性治疗策略的设计带来了挑战。此前，我们解析了METTL6的高分辨率冷冻电镜（cryo-EM）结构，揭示了其对丝氨酸tRNA产生底物特异性的分子机制。本研究后续将针对同家族的m³C tRNA甲基转移酶METTL2与METTL8的底物识别机制展开分析。