HETERONUCLEAR MULTIDIMENSIONAL NMR STUDIES OF RNA

RNA 的异核多维核磁共振研究

• 批准号: 2057069
• 负责人: ARTHUR PARDI
• 金额: $ 6.71万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-30 至 1996-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2057069
• 关键词: antibody receptor; endonuclease; heterogeneous nuclear RNA; interleukin 1; messenger RNA; nuclear magnetic resonance spectroscopy; nucleic acid sequence; nucleic acid structure; protein structure; technology /technique development; transfer RNA

This award will provide salary support that will significantly reduce the teaching load of the candidate and therefore will allow much more effort to be devoted to research on solution structural studies of RNAs. Specifically, the award will cut the teaching load of the candidate in half from the normal two (3 credit) courses per year to a single course. This reduced teaching load means that the candidate can take full advantage of unique research opportunities that the University of Colorado at Boulder offers for studies of RNA structure. Boulder has eight research groups that are extremely active in the areas of RNA biochemistry and molecular biology. The candidate moved to Boulder in 1988 to take advantage of this environment and since that time has set up a research effort in nuclear magnetic resonance (NMR) structural studies of RNA. This work complements the previous research by the candidate in the areas of NMR studies of DNA and antimicrobial peptides. The increased time that be devoted to research by this reduction of teaching load will allow the next phase of the NMR structural studies of RNA to proceed at an accelerated pace. This phase will involve application of heteronuclear multi-dimensional NMR experiments to the structure determination of biologically active RNAs. The heteronuclear NMR experiments are presently revolutionizing solution structure determinations of proteins, but these techniques have yet to be applied to studies of RNAs. The RNAs that will be studied include: i) two RNA enzymes, the self-cleaving hammerhead and hairpin RNA domains, both of which have potentially important in vivo applications as site-specific RNA endonucleases which can be designed to specifically cleave a target mRNA or the genome of an RNA virus such as HIV; ii) a yeast tRNA(Phe) system that will serve as a model system for developing techniques for identification of tertiary interactions in RNAs; and iii) several RNA structural motifs including a set of unusually stable and naturally occurring RNA hairpins that contain tetranucleotide loops. The structural information provided by the NMR experiments will be combined with additional biological and biochemical data in order to improve structure-activity relationships for RNAs.

该奖项将提供薪水支持，将大大减少 候选人的教学负载，因此将允许更多的努力 致力于研究RNA的溶液结构研究。 具体而言，该奖项将减少候选人的教学负担一半 从正常的两个（3个学分）课程到一门课程。 这 减少教学负荷意味着候选人可以充分利用 科罗拉多大学博尔德分校的独特研究机会 用于研究RNA结构的优惠。 博尔德有八个研究小组 在RNA生物化学和分子领域非常活跃 生物学。 候选人于1988年搬到博尔德（Boulder）利用这一点 环境，从那时起就建立了核研究工作 RNA的磁共振（NMR）结构研究。 这项工作补充 候选人在NMR研究领域的先前研究 和抗菌肽。 专用于研究的时间增加 通过减少教学负荷将允许NMR的下一阶段 RNA的结构研究以加速的速度进行。 这个阶段 将涉及杂核多维NMR实验的应用 到生物活性RNA的结构测定。 这 异核NMR实验目前正在革新解决方案 蛋白质的结构确定，但是这些技术尚未 应用于RNA的研究。 将研究的RNA包括：i）两个 RNA酶，自我切换的锤头和发夹RNA域，两个 作为位点特异性RNA的体内应用中可能重要的重要 核酸内切酶，可以专门裂解目标mRNA或 RNA病毒的基因组，例如HIV； ii）酵母tRNA（PHE）系统 将用作开发识别技术的模型系统 RNA中的三级相互作用； iii）几个RNA结构基序 包括一组异常稳定且自然存在的RNA发夹 包含四核苷酸环。 提供的结构信息由 NMR实验将与其他生物学和 生化数据，以改善结构活性关系 RNA。