Department of Structural Chemistry and Biology of Nucleic Acids, Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704 Poznan, Poland.
Int J Mol Sci. 2021 Feb 22;22(4):2176. doi: 10.3390/ijms22042176.
Methyltransferase-like protein 16 (METTL16) is a human RNA methyltransferase that installs mA marks on U6 small nuclear RNA (U6 snRNA) and -adenosylmethionine (SAM) synthetase pre-mRNA. METTL16 also controls a significant portion of mA epitranscriptome by regulating SAM homeostasis. Multiple molecular structures of the N-terminal methyltransferase domain of METTL16, including apo forms and complexes with -adenosylhomocysteine (SAH) or RNA, provided the structural basis of METTL16 interaction with the coenzyme and substrates, as well as indicated autoinhibitory mechanism of the enzyme activity regulation. Very recent structural and functional studies of vertebrate-conserved regions (VCRs) indicated their crucial role in the interaction with U6 snRNA. METTL16 remains an object of intense studies, as it has been associated with numerous RNA classes, including mRNA, non-coding RNA, long non-coding RNA (lncRNA), and rRNA. Moreover, the interaction between METTL16 and oncogenic lncRNA MALAT1 indicates the existence of METTL16 features specifically recognizing RNA triple helices. Overall, the number of known human mA methyltransferases has grown from one to five during the last five years. METTL16, CAPAM, and two rRNA methyltransferases, METTL5/TRMT112 and ZCCHC4, have joined the well-known METTL3/METTL14. This work summarizes current knowledge about METTL16 in the landscape of human mA RNA methyltransferases.
甲基转移酶样蛋白 16（METTL16）是一种人类 RNA 甲基转移酶，可在 U6 小核 RNA（U6 snRNA）和 -腺苷甲硫氨酸（SAM）合成酶前体 RNA 上安装 mA 标记。METTL16 还通过调节 SAM 平衡来控制大量的 mA 转录后修饰组。METTL16 的 N 端甲基转移酶结构域的多个分子结构，包括 apo 形式和与 -腺苷同型半胱氨酸（SAH）或 RNA 的复合物，为 METTL16 与辅酶和底物的相互作用提供了结构基础，并表明了该酶活性调节的自动抑制机制。最近对脊椎动物保守区（VCRs）的结构和功能研究表明，它们在与 U6 snRNA 的相互作用中起着至关重要的作用。METTL16 仍然是一个研究热点，因为它与包括 mRNA、非编码 RNA、长非编码 RNA（lncRNA）和 rRNA 在内的许多 RNA 类有关。此外，METTL16 与致癌 lncRNA MALAT1 的相互作用表明 METTL16 具有特定识别 RNA 三螺旋的特征。总的来说，在过去五年中，已知的人类 mA 甲基转移酶的数量从一个增加到了五个。METTL16、CAPAM 和两个 rRNA 甲基转移酶 METTL5/TRMT112 和 ZCCHC4 与著名的 METTL3/METTL14 一起加入。这项工作总结了当前关于人类 mA RNA 甲基转移酶中 METTL16 的知识。
