Institute of Molecular Biology and Tumor Research, Philipps University Marburg, 35043 Marburg, Germany.
Genes (Basel). 2022 Dec 8;13(12):2312. doi: 10.3390/genes13122312.
The RNA methylation of adenosine at the N6-position (mA) has attracted significant attention because of its abundance and dynamic nature. It accounts for more than 80% of all RNA modifications present in bacteria and eukaryotes and regulates crucial aspects of RNA biology and gene expression in numerous biological processes. The majority of mA found in mammals is deposited by a multicomponent complex formed between methyltransferase-like (METTL) proteins METTL3 and METTL14. In the last few years, the list of mA writers has grown, resulting in an expansion of our understanding of the importance of mA and the methylation machinery. The characterization of the less familiar family member METTL16 has uncovered a new function of the mA methylation apparatus, namely the fine-tuning of the cellular levels of the major methyl donor S-adenosylmethionine (SAM). METTL16 achieves this by adjusting the levels of the enzyme that synthesizes SAM in direct response to fluctuations in the SAM availability. This review summarizes recent progress made in understanding how METTL16 can sense and relay metabolic information and considers the wider implications. A brief survey highlights similarities and differences between METTL16 and the better-known METTL3/14 complex, followed by a discussion of the target specificity, modes of action and potential roles of METTL16.
N6-腺苷甲基化（m6A）的 RNA 修饰因其丰度和动态性质而受到广泛关注。它占细菌和真核生物中所有 RNA 修饰的 80%以上，调节着许多生物过程中 RNA 生物学和基因表达的关键方面。哺乳动物中大多数 mA 是由甲基转移酶样（METTL）蛋白 METTL3 和 METTL14 组成的多成分复合物形成的。在过去的几年中，m6A 写作者的名单不断增加，这使得我们对 mA 和甲基化机制的重要性的理解得到了扩展。对不太熟悉的成员 METTL16 的特征描述揭示了 mA 甲基化装置的一个新功能，即精细调节主要甲基供体 S-腺苷甲硫氨酸（SAM）的细胞水平。METTL16 通过直接响应 SAM 可用性的波动来调整合成 SAM 的酶的水平来实现这一点。这篇综述总结了最近在理解 METTL16 如何感知和传递代谢信息方面取得的进展，并考虑了更广泛的影响。简要调查突出了 METTL16 和更为人熟知的 METTL3/14 复合物之间的相似之处和不同之处，随后讨论了 METTL16 的靶标特异性、作用模式和潜在作用。
