The In Vivo and In Vitro Architecture of the Hepatitis C Virus RNA Genome Uncovers Functional RNA Secondary and Tertiary Structures.
The In Vivo and In Vitro Architecture of the Hepatitis C Virus RNA Genome Uncovers Functional RNA Secondary and Tertiary Structures.
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DOI：
10.1128/jvi.01946-21
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发表时间：
2022-04-27
影响因子：
5.4
通讯作者：
Pyle, Anna Marie
中科院分区：
文献类型：
--
作者：
Wan, Han;Adams, Rebecca L.;Lindenbach, Brett D.;Pyle, Anna Marie
丙型肝炎病毒（HCV）是一种正链RNA病毒，仍然是全球慢性肝脏疾病的主要病因之一。过去30年的研究表明，HCV含有高度结构化的RNA基因组，其中许多结构在HCV生命周期中起着重要作用。尽管核糖核酸调控在这种病毒中的重要性，大多数HCV RNA基因组的功能仍然没有研究。在这里，我们报告了一个完整的二级结构图的HCV RNA基因组在体内，这是研究在平行的二级结构相同的RNA在体外获得。我们的研究结果表明，HCV是广泛折叠的细胞背景下。通过对体内数据和体外数据进行全面的结构分析，我们确定了整个基因组的紧凑和保守的二级和三级结构。遗传和进化功能分析表明，许多这些元素在病毒的生命周期中发挥重要作用。除了提供一个全面的地图的RNA结构和核糖核酸调控元件在HCV，这项工作提供了一个资源，为未来的研究，旨在确定治疗靶点，并进行进一步的机制研究，这一重要的人类病原体。重要性HCV是迄今为止研究的结构最高度的RNA基因组之一，它是研究RNA结构在蛋白质编码基因中作用的有价值的模型系统。虽然先前的研究已经确定了HCV基因组内调节RNA结构的个别情况，但HCV基因组的全长结构尚未在体内确定。在这里，我们提出了完整的二级结构图确定在细胞和相应的转录体外产生的HCV。除了提供整个基因组RNA的功能性二级结构元件的全面图谱外，我们还确定了一组新的三级相互作用，并证明了它们的功能重要性。就更广泛的意义而言，本研究中开发的管道可以应用于其他长RNA，例如长非编码RNA。此外，在这项研究中的RNA结构基序的特点拓宽了已知的核糖核酸调控元件的剧目。
Hepatitis C virus (HCV) is a positive-strand RNA virus that remains one of the main contributors to chronic liver disease worldwide. Studies over the last 30 years have demonstrated that HCV contains a highly structured RNA genome and many of these structures play essential roles in the HCV life cycle. Despite the importance of riboregulation in this virus, most of the HCV RNA genome remains functionally unstudied. Here, we report a complete secondary structure map of the HCV RNA genome in vivo, which was studied in parallel with the secondary structure of the same RNA obtained in vitro. Our results show that HCV is folded extensively in the cellular context. By performing comprehensive structural analyses on both in vivo data and in vitro data, we identify compact and conserved secondary and tertiary structures throughout the genome. Genetic and evolutionary functional analyses demonstrate that many of these elements play important roles in the virus life cycle. In addition to providing a comprehensive map of RNA structures and riboregulatory elements in HCV, this work provides a resource for future studies aimed at identifying therapeutic targets and conducting further mechanistic studies on this important human pathogen. IMPORTANCE HCV has one of the most highly structured RNA genomes studied to date, and it is a valuable model system for studying the role of RNA structure in protein-coding genes. While previous studies have identified individual cases of regulatory RNA structures within the HCV genome, the full-length structure of the HCV genome has not been determined in vivo. Here, we present the complete secondary structure map of HCV determined both in cells and from corresponding transcripts generated in vitro. In addition to providing a comprehensive atlas of functional secondary structural elements throughout the genomic RNA, we identified a novel set of tertiary interactions and demonstrated their functional importance. In terms of broader implications, the pipeline developed in this study can be applied to other long RNAs, such as long noncoding RNAs. In addition, the RNA structural motifs characterized in this study broaden the repertoire of known riboregulatory elements.
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影响因子：
16
作者：
Huston NC;Wan H;Strine MS;de Cesaris Araujo Tavares R;Wilen CB;Pyle AM
通讯作者：
Pyle AM
影响因子：
14.9
作者：
Borman, AM;LeMercier, P;Kean, KM
通讯作者：
Kean, KM
DOI：
10.1073/pnas.1219988110
发表时间：
2013-04-02
影响因子：
11.1
作者：
Hajdin, Christine E.;Bellaousov, Stanislav;Weeks, Kevin M.
通讯作者：
Weeks, Kevin M.
影响因子：
5.4
作者：
Kolykhalov, AA;Mihalik, K;Rice, CM
通讯作者：
Rice, CM
影响因子：
10.7
作者：
Kumar, Sudhir;Stecher, Glen;Tamura, Koichiro
通讯作者：
Tamura, Koichiro