A discontinuous RNA platform mediates RNA virus replication: building an integrated model for RNA-based regulation of viral processes.
A discontinuous RNA platform mediates RNA virus replication: building an integrated model for RNA-based regulation of viral processes.
复制标题
DOI：
10.1371/journal.ppat.1000323
复制
发表时间：
2009-03
期刊：
影响因子：
6.7
通讯作者：
White KA
中科院分区：
文献类型：
--
作者：
Wu B;Pogany J;Na H;Nicholson BL;Nagy PD;White KA
正链RNA病毒在其基因组内含有介导多种基本病毒过程的RNA元件。传统的观点认为这些元素是局部RNA结构。然而，由于越来越多地发现功能性病毒RNA元件，这种观点正在发生变化，这些元件是由远距离RNA-RNA相互作用形成的，通常跨越数千个核苷酸。番茄丛矮病毒的正链RNA基因组通过具有不同的长程RNA-RNA相互作用来调节病毒的翻译和转录，从而验证了这一概念。在这里，我们报告说，第三个基本的绒毛丛矮病毒的过程，病毒基因组复制，需要一个长距离的RNA为基础的相互作用跨越3000 nts。体内和体外分析表明，由相互作用形成的不连续RNA平台促进病毒RNA复制酶的有效组装。这一发现使我们能够建立一个整体RNA结构在调节真核RNA病毒繁殖中的作用的综合模型，并且所获得的见解扩展了我们对病毒RNA基因组多功能性质的理解。正链（即信使感应的）RNA病毒负责植物和动物中的重大疾病。这些病毒的单链RNA基因组作为病毒蛋白翻译的模板，并执行其他基本功能，这些功能通常涉及局部RNA结构，如RNA发夹。有趣的是，植物番茄丛矮病毒利用许多长距离的基因组内RNA-RNA相互作用来调节其宿主感染期间的重要事件，即病毒翻译和转录。在这里，我们报告说，一个额外的重要的绒毛丛矮病毒过程，病毒RNA复制，也需要一个长距离的RNA-RNA相互作用。我们的分析表明这种基于RNA的相互作用在病毒复制酶组装中的作用，该复制酶负责执行病毒RNA合成。这些信息被用来生成一个全面的高阶RNA结构模型，在这个真核RNA病毒的基因组中的功能性长程相互作用。该模型强调了全球RNA结构在成功感染宿主所必需的多个病毒过程中的关键作用。
Plus-strand RNA viruses contain RNA elements within their genomes that mediate a variety of fundamental viral processes. The traditional view of these elements is that of local RNA structures. This perspective, however, is changing due to increasing discoveries of functional viral RNA elements that are formed by long-range RNA–RNA interactions, often spanning thousands of nucleotides. The plus-strand RNA genomes of tombusviruses exemplify this concept by possessing different long-range RNA–RNA interactions that regulate both viral translation and transcription. Here we report that a third fundamental tombusvirus process, viral genome replication, requires a long-range RNA–based interaction spanning ∼3000 nts. In vivo and in vitro analyses suggest that the discontinuous RNA platform formed by the interaction facilitates efficient assembly of the viral RNA replicase. This finding has allowed us to build an integrated model for the role of global RNA structure in regulating the reproduction of a eukaryotic RNA virus, and the insights gained have extended our understanding of the multifunctional nature of viral RNA genomes. Plus-strand (i.e. messenger-sensed) RNA viruses are responsible for significant diseases in plants and animals. The single-stranded RNA genomes of these viruses serve as templates for translation of viral proteins and perform other essential functions that generally involve local RNA structures, such as RNA hairpins. Interestingly, plant tombusviruses utilize a number of long-range intra-genomic RNA–RNA interactions to regulate important events during infection of their hosts, i.e. viral translation and transcription. Here, we report that an additional essential tombusvirus process, viral RNA replication, also requires a long-range RNA–RNA interaction. Our analyses indicate a role for this RNA–based interaction in the assembly of the viral replicase, which is responsible for executing viral RNA synthesis. This information was used to generate a comprehensive higher-order RNA structural model for functional long-range interactions in the genome of this eukaryotic RNA virus. The model highlights a critical role for global RNA structure in multiple viral processes that are necessary for successful infection of hosts.
登录
查看更多内容
影响因子：
4.5
作者：
Fabian, Marc R.;White, K. Andrew
通讯作者：
White, K. Andrew
影响因子：
4.8
作者：
Fabian, MR;White, KA
通讯作者：
White, KA
影响因子：
5.4
作者：
Kofler, RM;Hoenninger, VM;Mandl, CW
通讯作者：
Mandl, CW
影响因子：
3.8
作者：
Burgyan, J;Rubino, L;Russo, M
通讯作者：
Russo, M
DOI：
10.1073/pnas.84.22.8140
发表时间：
1987-11-01
影响因子：
11.1
作者：
HSU, MT;PARVIN, JD;PALESE, P
通讯作者：
PALESE, P