The Center for HIV RNA Studies (CRNA)

艾滋病毒核糖核酸研究中心(CRNA)将专注于确定 HIV-1RNA依赖的复制在细胞、病毒和原子水平上起作用。虽然相当可观 在过去的25年里，在了解蛋白质如何在HIV-1复制中发挥作用方面取得了进展， 关于HIV-1RNA的结构、动态、贩运以及与 蛋白质使病毒能够复制。尽管HIV-1RNA具有异常丰富的生物学功能，但缺乏 对这些生物功能是如何执行的详细机械洞察力是由于固有的困难 研究RNA分子的结构和动力学。例如，它一直是具有挑战性的获得 利用传统X射线获得RNA和蛋白质-RNA复合体的高分辨结构信息 结晶学、核磁共振或低温电子显微镜方法。研究这一问题也很困难。 体外和细胞内RNA分子与蛋白质的功能和相互作用。CRNA由一个 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，他们中的许多人是研究艾滋病毒-1RNA及其结构作用的领导者 在病毒复制方面。他们已经开发并将进一步推进新的方法，以克服目前的 技术障碍，使得能够机械性地确定艾滋病毒-1RNA结构和 病毒转录、剪接、翻译、包装、颗粒组装和相互作用中的相关蛋白 有限制因素的。本文提出的研究将使CRNA能够推进临床目标 相关性，包括开发新的抗病毒化合物，设计新的抗病毒战略 重新激活潜伏的前病毒，增强宿主对艾滋病毒感染的防御。这些研究 还将导致新技术的发展，这些技术可以应用于RNA生物学的所有领域。

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.