A N7-guanine RNA cap methyltransferase signature-sequence as a genetic marker of large genome, non-mammalian Tobaniviridae
A N7-guanine RNA cap methyltransferase signature-sequence as a genetic marker of large genome, non-mammalian Tobaniviridae
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DOI：
10.1093/nargab/lqz022
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发表时间：
2020-03-01
影响因子：
4.6
通讯作者：
Canard, Bruno
中科院分区：
文献类型：
--
作者：
Ferron, Francois;Debat, Humberto J.;Canard, Bruno
巢病毒目是一组多样化的（+）RNA病毒，根据它们共同的基因组结构和保守的复制酶分类在一起，尽管大小和复杂性存在巨大差异。一个这样的差异涉及负责产生所提出的病毒5' RNA帽的机制和酶。在冠状病毒科中，两种单独的甲基转移酶（MTase）nsp 14和nsp 16分别进行RNA帽N7-鸟嘌呤和2 '-OH甲基化以产生所提出的m7 GpppNm I型帽结构。对于巢病毒目中的大多数其他科，涉及5'加帽的存在、结构和关键酶远不清楚。这些病毒要么完全缺乏RNA MTase特征序列，要么缺乏N7-鸟嘌呤甲基转移酶特征序列，这模糊了我们对这些家族的RNA帽如何被N7-甲基化的理解。在这里，我们报告发现了一个假定的Rossmann折叠RNA甲基转移酶在10 Tobaniviridae成员在Orf 1a，一个不寻常的基因组位点，这个基因。多重序列比对和结构分析使我们提出这个新的基因作为一个典型的RNA帽N7-鸟嘌呤MTase与底物特异性和活性位点组织类似的典型真核RNA帽N7-鸟嘌呤MTase。
The order Nidovirales is a diverse group of (+)RNA viruses, classified together based on their common genome organisation and conserved replicative enzymes, despite drastic differences in size and complexity. One such difference pertains to the mechanisms and enzymes responsible for generation of the proposed viral 5' RNA cap. Within the Coronaviridae family, two separate methytransferases (MTase), nsp14 and nsp16, perform the RNA-cap N7-guanine and 2'-OH methylation respectively for generation of the proposed m7GpppNm type I cap structure. For the majority of other families within the Nidovirales order, the presence, structure and key enzymes involved in 5' capping are far less clear. These viruses either lack completely an RNA MTase signature sequence, or lack an N7-guanine methyltransferase signature sequence, obscuring our understanding about how RNA-caps are N7-methylated for these families. Here, we report the discovery of a putative Rossmann fold RNA methyltransferase in 10 Tobaniviridae members in Orf1a, an unusual genome locus for this gene. Multiple sequence alignments and structural analyses lead us to propose this novel gene as a typical RNA-cap N7-guanine MTase with substrate specificity and active-site organization similar to the canonical eukaryotic RNA-cap N7-guanine MTase.