The structure and functions of coronavirus genomic 3' and 5' ends.
The structure and functions of coronavirus genomic 3' and 5' ends.
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DOI：
10.1016/j.virusres.2015.02.025
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发表时间：
2015-08-03
期刊：
影响因子：
5
通讯作者：
Leibowitz JL
中科院分区：
文献类型：
--
作者：
Yang D;Leibowitz JL
提出了保守的 5' 和 3' β 冠状病毒顺式作用 RNA 二级结构模型。冠状病毒复制所需的 5' 顺式作用序列延伸至第一个开放阅读框。冠状病毒复制所需的所有 3' 顺式作用序列都包含在 3'UTR 中。冠状病毒 3'UTR 中存在假定的分子开关。回顾了与这些顺式作用区域相互作用的蛋白质。冠状病毒（CoV）是人类和动物疾病的重要原因。大多数人类冠状病毒通常会引起相对轻微的呼吸道疾病；然而，两种人畜共患的冠状病毒，SARS-CoV 和 MERS-CoV，可导致严重疾病和死亡。过去 35 年的研究阐明了冠状病毒复制的许多方面。本综述的重点是 β 冠状病毒基因组 5' 和 3' 端保守 RNA 二级结构的功能分析。 5' 350个核苷酸折叠成一组保守的RNA二级结构，反向遗传学研究表明这些结构在β冠状病毒亚基因组RNA的不连续合成中发挥着重要作用。这些顺式作用元件将 5'UTR 的 3' 延伸到 ORF1a 中。 3'UTR 同样保守，包含病毒复制所需的所有顺式作用序列。 3'UTR 5' 端附近的两个竞争构象已被证明可以构成潜在的分子开关。有一些证据表明 3'UTR 和 5'UTR 之间的关联对于亚基因组 RNA 合成是必要的，但这种关联的基础尚不清楚。许多宿主 RNA 蛋白已被证明可与 5' 和 3' 顺式作用区域结合，但这些在病毒复制中的重要性尚不清楚。两种病毒蛋白已被鉴定为与 5' 顺式作用区域结合，即 nsp1 和 N 蛋白。 nsp8 和 nsp9 与包含推定分子开关的 3'UTR 区域之间的遗传相互作用表明这两种蛋白质与该区域结合。
Models of conserved 5′ and 3′ betacoronavirus cis-acting RNA secondary structures are presented. The 5′ cis-acting sequences required for coronavirus replication extend into the first open reading frame. All 3′ cis-acting sequences required for coronavirus replication are contained in the 3′UTR. A putative molecular switch is present in the coronavirus 3′UTR. Proteins interacting with these cis-acting regions are reviewed. Coronaviruses (CoVs) are an important cause of illness in humans and animals. Most human coronaviruses commonly cause relatively mild respiratory illnesses; however two zoonotic coronaviruses, SARS-CoV and MERS-CoV, can cause severe illness and death. Investigations over the past 35 years have illuminated many aspects of coronavirus replication. The focus of this review is the functional analysis of conserved RNA secondary structures in the 5′ and 3′ of the betacoronavirus genomes. The 5′ 350 nucleotides folds into a set of RNA secondary structures which are well conserved, and reverse genetic studies indicate that these structures play an important role in the discontinuous synthesis of subgenomic RNAs in the betacoronaviruses. These cis-acting elements extend 3′ of the 5′UTR into ORF1a. The 3′UTR is similarly conserved and contains all of the cis-acting sequences necessary for viral replication. Two competing conformations near the 5′ end of the 3′UTR have been shown to make up a potential molecular switch. There is some evidence that an association between the 3′ and 5′UTRs is necessary for subgenomic RNA synthesis, but the basis for this association is not yet clear. A number of host RNA proteins have been shown to bind to the 5′ and 3′ cis-acting regions, but the significance of these in viral replication is not clear. Two viral proteins have been identified as binding to the 5′ cis-acting region, nsp1 and N protein. A genetic interaction between nsp8 and nsp9 and the region of the 3′UTR that contains the putative molecular switch suggests that these two proteins bind to this region.
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