A comprehensive review of m6A/m6Am RNA methyltransferase structures.
A comprehensive review of m6A/m6Am RNA methyltransferase structures.
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DOI：
10.1093/nar/gkab378
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发表时间：
2021-07-21
影响因子：
14.9
通讯作者：
Tisné C
中科院分区：
文献类型：
--
作者：
Oerum S;Meynier V;Catala M;Tisné C
基因表达在许多水平上受到调节，包括共转录或转录后，其中在核糖和碱基上向RNA添加化学修饰。通过RNA修饰的表达控制被称为“表观转录组学”，以与DNA修饰的相关“表观基因组学”保持一致。一种这样的RNA修饰是在大多数类型的RNA中的腺苷（m6 A）和2′-O-甲基腺苷（m6 Am）上发现的N6-甲基化。N6-甲基化可以影响修饰的RNA的折叠、稳定性、降解和细胞相互作用，涉及其在诸如剪接、翻译、输出和衰变的过程中。这种修饰所起的多重作用解释了为什么m6 A失调与多种人类癌症有关。m6 A/m6 Am书写酶是RNA甲基转移酶（MTases）。可获得来自人（m6 A mRNA、m6 A snRNA、m6 A rRNA和m6 Am mRNA MTase）、斑马鱼（m6 Am mRNA MTase）和细菌（m6 A rRNA MTase）的功能性表征的m6 A RNA MTase的结构。对于这些MTase中的每一个，我们描述了它们的整体结构域组织，活性位点架构和底物结合。我们确定了仍有待研究的领域，提出尚未探索的路线MTase的结构表征：底物复合物，并强调共同的结构元素，应描述为未来的m6 A/m6 Am RNA MTase结构。
Gene expression is regulated at many levels including co- or post-transcriptionally, where chemical modifications are added to RNA on riboses and bases. Expression control via RNA modifications has been termed ‘epitranscriptomics’ to keep with the related ‘epigenomics’ for DNA modification. One such RNA modification is the N6-methylation found on adenosine (m6A) and 2′-O-methyladenosine (m6Am) in most types of RNA. The N6-methylation can affect the fold, stability, degradation and cellular interaction(s) of the modified RNA, implicating it in processes such as splicing, translation, export and decay. The multiple roles played by this modification explains why m6A misregulation is connected to multiple human cancers. The m6A/m6Am writer enzymes are RNA methyltransferases (MTases). Structures are available for functionally characterized m6A RNA MTases from human (m6A mRNA, m6A snRNA, m6A rRNA and m6Am mRNA MTases), zebrafish (m6Am mRNA MTase) and bacteria (m6A rRNA MTase). For each of these MTases, we describe their overall domain organization, the active site architecture and the substrate binding. We identify areas that remain to be investigated, propose yet unexplored routes for structural characterization of MTase:substrate complexes, and highlight common structural elements that should be described for future m6A/m6Am RNA MTase structures.
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影响因子：
14.9
作者：
BRANLANT, C;KROL, A;EBEL, JP
通讯作者：
EBEL, JP
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Fray RG
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通讯作者：
Vallier L
影响因子：
14.9
作者：
BRANLANT, C;KROL, A;KOSSEL, H
通讯作者：
KOSSEL, H