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Abstract：
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.
摘要：
基因表达在许多水平上受到调控，包括协同或转录后，其中化学修饰被添加到核糖和碱基上的RNA。通过RNA修饰进行的表达控制被称为“表观遗传学”，以与相关的“表观基因组学”进行DNA修饰。一种这样的RNA修饰是在大多数类型的RNA中的腺苷(m6A)和2'-O-甲基腺苷(m6Am)上发现的N6-甲基化。N6甲基化可以影响折叠，稳定性,修饰的RNA的降解和细胞相互作用，将其包含在拼接等过程中，翻译,出口和衰变。这种修饰所扮演的多重角色解释了为什么m6A失调与多种人类癌症有关。m6A/m6Am写入酶是RNA甲基转移酶(MTases)。结构可用于来自人的功能表征的m6ARNAMTases(m6AmRNA，m6AsnRNA，m6ArRNA和m6AmmRNAMTases)，斑马鱼(m6AmmRNAMTase)和细菌(m6ArRNAMTase)。对于这些MTases中的每一个，我们描述了他们的整体领域组织，活性位点结构和底物结合。我们确定了仍有待调查的领域，提出了尚未探索的MTase结构表征途径：底物复合物，并强调了未来m6A/m6AmRNAMTase结构应描述的常见结构元件。
