The Center for HIV RNA Studies (CRNA)

HIV RNA 研究中心 (CRNA)

• 批准号: 8410210
• 负责人: ALICE TELESNITSKY
• 金额: $ 445.34万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-17 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8410210
• 关键词: Acquired Immunodeficiency Syndrome; Antiviral Agents; Area; Behavior; Binding; Binding Sites; Biochemical; Biological Process; Biology; Cell Culture Techniques; Cells; Cellular Structures; Complex; Crystallography; Development; Electrons; Elements; Feasibility Studies; Fluorescence Microscopy; Fractionation; Gagging; Gene Expression; Genetic Transcription; Genomics; Goals; HIV; HIV Infections; HIV-1; Host Defense; Human; Hybrids; Image; Immunoprecipitation; In Vitro; Integration Host Factors; Isotopes; Lead; Life; Ligands; Maps; Measures; Methodology; Methods; Microscopic; Microscopy; Molecular; Molecular Structure; Monitor; Movement; Mutagenesis; Mutation; Optics; Phylogenetic Analysis; Physical condensation; Play; Post-Transcriptional Regulation; Process; Production; Property; Proteins; Proviruses; RNA; RNA Binding; RNA Sequences; RNA Splicing; RNA helicase A; RNA-Protein Interaction; Regulation; Resolution; Roentgen Rays; Role; Structural Biologist; Structural Protein; Structure; Techniques; Technology; Testing; Transcriptional Regulation; Translations; Viral; Virion; Virus Replication; X-Ray Crystallography; base; clinically relevant; computerized tools; crosslink; design; human disease; inhibitor/antagonist; innovation; insight; interest; multidisciplinary; next generation; novel; novel strategies; optical imaging; particle; protein complex; protein function; protein structure; research study; small molecule; tool; trafficking; viral RNA; virtual

DESCRIPTION (provided by applicant): The Center for HIV RNA Studies (CRNA) will focus on determining the structural and mechanistic bases of HIV-1 RNA dependent replication functions at the cellular, viral and atomic levels. Although considerable progress has been made over the past 25 years in understanding how proteins function in HIV-1 replication, comparatively little is known about how HIV-1 RNA structure, dynamics, trafficking, and interactions with proteins enable virus replication. Although HIV-1 RNA is exceptionally rich in biological functions, the paucity of detailed mechanistic insight into how these biological functions are executed is due to inherent difficulties in studying the structure and dynamics of RNA molecules. For example, it has been challenging to obtain high-resolution structural information for RNA and protein-RNA complexes using traditional X-ray crystallographic, NMR or cryo-electron microscopic approaches. It has also been difficult to study the functions and interactions of RNA molecules with proteins in vitro and in cells. The CRNA consists of a multidisciplinary team of structural biologists, chemists, cell and computational biologists, molecular biologists and virologists, many of whom are leaders in the study of HIV-1 RNA and the role of its structures in virus replication. They have developed and will further advance new approaches to overcome current technological obstacles, enabling mechanistic determination of the role of HIV-1 RNA structures and associated proteins in viral transcription, splicing, translation, packaging, particle assembly and interactions with restriction factors. The studies proposed herein will enable the CRNA to advance goals of clinical relevance, including the development of novel antiviral compounds, design of new strategies for the reactivation of latent proviruses, and the augmentation of host defenses against HIV infection. These studies will also result in the development of novel techniques that can be applied to all areas of RNA biology. PUBLIC HEALTH RELEVANCE: Although much is known about how protein structures contribute to HIV-1 replication, little is known about the structures, dynamics and mechanistic roles played by viral RNA. Structural studies of RNAs are technically challenging, but are of key importance in understanding many biological processes, and could ultimately lead to the development of new approaches for the treatment of AIDS and many other human diseases.

描述（由申请人提供）：HIV RNA研究中心（CRNA）将专注于在细胞、病毒和原子水平上确定HIV-1 RNA依赖复制功能的结构和机制基础。尽管在过去的25年中，在了解蛋白质如何在HIV-1复制中发挥作用方面取得了相当大的进展，但对于HIV-1 RNA的结构、动力学、运输以及与蛋白质的相互作用如何使病毒复制知之甚少。尽管HIV-1 RNA具有异常丰富的生物学功能，但由于研究RNA分子结构和动力学的固有困难，缺乏对这些生物学功能如何执行的详细机制的了解。例如，利用传统的x射线晶体学、核磁共振或低温电子显微镜方法获得RNA和蛋白质-RNA复合物的高分辨率结构信息一直具有挑战性。在体外和细胞中研究RNA分子与蛋白质的功能和相互作用也很困难。CRNA由结构生物学家、化学家、细胞和计算生物学家、分子生物学家和病毒学家组成的多学科团队组成，其中许多人是HIV-1 RNA及其结构在病毒复制中的作用研究的领导者。他们已经开发并将进一步推进新方法，以克服当前的技术障碍，使机制确定HIV-1 RNA结构和相关蛋白在病毒转录，剪接，翻译，包装，颗粒组装和与限制因子相互作用中的作用。本文提出的研究将使CRNA能够推进临床相关目标，包括开发新型抗病毒化合物，设计潜伏前病毒重新激活的新策略，以及增强宿主对HIV感染的防御。这些研究也将导致新技术的发展，可应用于RNA生物学的所有领域。