Department of Biosciences, University of Oslo, PO Box 1066 Blindern, 0316Oslo, Norway.
CRESCO - Centre for Embryology and Healthy Development, University of Oslo and Oslo University Hospital, Oslo, Norway.
Nucleic Acids Res. 2024 Oct 28;52(19):11423-11441. doi: 10.1093/nar/gkae816.
Methylation is a common biochemical reaction, and a number of methyltransferase (MTase) enzymes mediate the various methylation events occurring in living cells. Almost all MTases use the methyl donor S-adenosylmethionine (AdoMet), and, in humans, the largest group of AdoMet-dependent MTases are the so-called seven-β-strand (7BS) MTases. Collectively, the 7BS MTases target a wide range of biomolecules, i.e. nucleic acids and proteins, as well as several small metabolites and signaling molecules. They play essential roles in key processes such as gene regulation, protein synthesis and metabolism, as well as neurotransmitter synthesis and clearance. A decade ago, roughly half of the human 7BS MTases had been characterized experimentally, whereas the remaining ones merely represented hypothetical enzymes predicted from bioinformatics analysis, many of which were denoted METTLs (METhylTransferase-Like). Since then, considerable progress has been made, and the function of > 80% of the human 7BS MTases has been uncovered. In this review, I provide an overview of the (estimated) 120 human 7BS MTases, grouping them according to substrate specificities and sequence similarity. I also elaborate on the challenges faced when studying these enzymes and describe recent major advances in the field.
甲基化是一种常见的生化反应，许多甲基转移酶（MTase）酶介导活细胞中发生的各种甲基化事件。几乎所有的 MTase 都使用甲基供体 S-腺苷甲硫氨酸（AdoMet），在人类中，最大的一组 AdoMet 依赖性 MTase 是所谓的七-β-链（7BS）MTase。总的来说，7BS MTase 靶向广泛的生物分子，即核酸和蛋白质，以及几种小代谢物和信号分子。它们在基因调控、蛋白质合成和代谢以及神经递质合成和清除等关键过程中发挥着重要作用。十年前，大约一半的人类 7BS MTase 已经通过实验进行了表征，而其余的仅仅代表了从生物信息学分析预测的假设酶，其中许多被称为 METTLs（甲基转移酶样）。自那时以来，已经取得了相当大的进展，已经揭示了 >80%的人类 7BS MTase 的功能。在这篇综述中，我概述了（估计）120 个人类 7BS MTase，根据底物特异性和序列相似性对它们进行分组。我还详细阐述了研究这些酶所面临的挑战，并描述了该领域最近的重大进展。
