Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing, China.
Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing, China.
J Biol Chem. 2021 Aug;297(2):100973. doi: 10.1016/j.jbc.2021.100973. Epub 2021 Jul 16.
N-methyladenosine (mA) is the most frequent chemical modification in eukaryotic mRNA and is known to participate in a variety of physiological processes, including cancer progression and viral infection. The reversible and dynamic mA modification is installed by mA methyltransferase (writer) enzymes and erased by mA demethylase (eraser) enzymes. mA modification recognized by mA binding proteins (readers) regulates RNA processing and metabolism, leading to downstream biological effects such as promotion of stability and translation or increased degradation. The mA writers and erasers determine the abundance of mA modifications and play decisive roles in its distribution and function. In this review, we focused on mA writers and erasers and present an overview on their known functions and enzymatic molecular mechanisms, showing how they recognize substrates and install or remove mA modifications. We also summarize the current applications of mA writers and erasers for mA detection and highlight the merits and drawbacks of these available methods. Lastly, we describe the biological functions of mA in cancers and viral infection based on research of mA writers and erasers and introduce new assays for mA functionality via programmable mA editing tools.
N6-甲基腺苷（m6A）是真核 mRNA 中最常见的化学修饰，已知其参与多种生理过程，包括癌症进展和病毒感染。可逆且动态的 m6A 修饰由 m6A 甲基转移酶（writer）酶进行安装，并由 m6A 去甲基化酶（eraser）酶进行擦除。m6A 结合蛋白（reader）识别的 m6A 修饰调节 RNA 加工和代谢，导致下游生物学效应，如促进稳定性和翻译或增加降解。m6A 的 writers 和 erasers 决定了 m6A 修饰的丰度，并在其分布和功能中起决定性作用。在这篇综述中，我们重点介绍了 m6A 的 writers 和 erasers，并概述了它们已知的功能和酶促分子机制，展示了它们如何识别底物并安装或去除 m6A 修饰。我们还总结了 m6A 的 writers 和 erasers 在 m6A 检测中的当前应用，并强调了这些可用方法的优点和缺点。最后，我们根据 m6A 的 writers 和 erasers 的研究描述了 m6A 在癌症和病毒感染中的生物学功能，并介绍了通过可编程 m6A 编辑工具进行 m6A 功能的新检测方法。
