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: 6434348
• 负责人: Andrew H Kaplan
• 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 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6434348
• 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.

描述（由申请人提供）：所有逆转录病毒的独特特征 迄今为止的研究表明，它们封装了相同正链的二聚体 基因组 RNA。逆转录病毒基因组RNA的二聚化起着关键作用 在病毒复制中；干扰病毒能力的突变 RNA 形成二聚体对感染性具有显着影响。 尽管这种高度特定的现象在所有领域都具有不变性 逆转录病毒系统，重要的生物学和结构问题仍然存在 没有得到答复。首先，二聚化在病毒生命中发挥的确切作用 周期模糊。包含二聚体的病毒基因组区域 连接结构包含顺式作用信号，这是必不可少的 全长病毒RNA的剪接、翻译和包装。研究 在我们的实验室进行的以及其他小组报告的结果表明 RNA 形成二聚体的能力可能会影响其中的任何一个或所有 病毒复制的步骤。其次，二聚体形成的机制也不是 最终二聚体的结构也尚未阐明。虽然有几个 研究小组认为二聚化是一个动态过程，涉及多个因素 决定因素，对于 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，如 以及成熟二聚体的结构。最后，鉴于我们的这些差距 的知识，对它们之间的相互作用的理解非常有限。 二聚体产生的过程、它们实现的最终结构以及 二聚体形成对生物功能的最终影响。 我们相信我们的研究将为 RNA 结构和 逆转录病毒生物学。具体来说，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 的二聚化和 这些结构组装成活性二聚体的机制。 三．定义二聚体结构与其功能之间的相互作用 在病毒生命周期中。