Retroviral Genomic RNA Dimer Structure and Function

逆转录病毒基因组 RNA 二聚体结构和功能

• 批准号: 6879018
• 负责人: JULIE AE NELSON
• 金额: $ 25.46万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6879018
• 关键词: Retroviridae; chemical structure function; dimer; gene mutation; molecular assembly /self assembly; mouse sarcoma virus; nucleic acid structure; polymerase chain reaction; virus RNA; virus genetics; virus replication

DESCRIPTION (provided by applicant): A unique feature of all retroviruses studied to date is that they encapsidate a dimer of identical positive-strand genomic RNAs. The dimerization of retroviral genomic RNA plays a critical role in viral replication; mutations that interfere with the ability of the viral RNA to form dimers have a dramatic effect on infectivity. Despite the invariant nature of this highly specific phenomenon across all retroviral systems, important biological and structural questions remain unanswered. First, the precise role(s) played by dimerization in the viral life cycle is obscure. The region of the viral genome that encompasses the dimer linkage structure contains cis-acting signals that are indispensable for splicing, translation and packaging of the full length viral RNA. Studies performed in our laboratories as well as those reported by other groups suggest that the ability of the RNA to form dimers may impact on any or all of these steps in viral replication. Second, neither the mechanism by which dimers form nor the structure of the final dimer has been elucidated. Although several groups have suggested that dimerization is a dynamic process involving several determinants, there is significant disagreement regarding the nature of the RNA determinants themselves, the order in which these determinants interact, as well as the structure of the mature dimer. Finally, given these gaps in our knowledge, there is a very limited understanding of the interaction between the process by which dimers arise, the final structure they achieve and the ultimate impact of dimer formation on biological function. We believe our studies will provide important insights into RNA structure and retroviral biology. Specifically, we will: I. Characterize the role played by dimerization of the viral genomic RNA in viral replication. II. Establish a detailed molecular understanding of the RNA structures required for dimerization of the Moloney murine sarcoma virus (MuSV) genomic RNA and the mechanism by which these structures assemble into an active dimer. III. Define the interaction between the structure of the dimer and its function in the viral life cycle.

性状（由申请人提供）：所有逆转录病毒的独特特征 迄今为止研究的是，它们使相同的正链的二聚体 基因组RNA。逆转录病毒基因组RNA的二聚化在 在病毒复制中;干扰病毒复制能力的突变 RNA形成二聚体对感染性有显著影响。 尽管这种高度特异性的现象在所有领域都是不变的， 逆转录病毒系统，重要的生物和结构问题仍然存在， 无人回应首先，二聚化在病毒生命中所起的确切作用 周期是模糊的。病毒基因组中包含二聚体的区域 连接结构包含顺式作用信号， 全长病毒RNA的剪接、翻译和包装。研究 在我们的实验室中进行的实验以及其他小组报告的实验表明， RNA形成二聚体的能力可能会影响任何或所有这些 病毒复制的步骤。其次，二聚体形成的机制 也没有阐明最终二聚体的结构。尽管几 研究小组认为，二聚化是一个动态过程，涉及几个 决定因素，关于RNA的性质存在重大分歧， 决定因素本身，这些决定因素相互作用的顺序， 以及成熟二聚体的结构。最后，考虑到我们的这些差距， 知识，有一个非常有限的理解之间的相互作用， 二聚体产生的过程，它们达到的最终结构和 二聚体形成对生物学功能的最终影响。 我们相信我们的研究将为RNA结构提供重要见解， 逆转录病毒生物学具体而言，我们将： I.表征病毒基因组RNA二聚化在 病毒复制 二.建立对所需RNA结构的详细分子理解 用于莫洛尼鼠肉瘤病毒（MuSV）基因组RNA的二聚化， 这些结构组装成活性二聚体的机制。 三.定义二聚体的结构与其功能之间的相互作用 在病毒的生命周期中。