RNA FOLDING STRUCTURE AND KINETICS

RNA 折叠结构和动力学

• 批准号: 8361267
• 负责人: ROBERT BRIBER
• 金额: $ 6.52万
• 依托单位: ILLINOIS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361267
• 关键词: Area; Azoarcus; Bacteria; Biophysics; Cations; Cells; Charge; Crowding; Electrostatics; Funding; Gene Expression Regulation; Grant; Introns; Kinetics; Microscopic; Molecular; National Center for Research Resources; Physiological; Principal Investigator; Process; RNA; RNA Folding; RNA Processing; RNA Sequences; RNA replication; Research; Research Infrastructure; Resources; Roentgen Rays; Role; Source; Specificity; Structure; Tetrahymena; Theoretical model; Thermodynamics; Time; United States National Institutes of Health; Work; base; cost; group I ribozyme; inorganic phosphate; insight; mutant; protein complex; viral RNA

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Folding of RNA molecules is critical for the functioning of a range of processes in cells, including gene regulation, viral RNA replication, and the assembly of RNA-protein complexes. As part of these processes, RNA must fold into a specific native structure. The folding of RNA starts with the neutralization of negatively charged phosphate groups in RNA by cations. The charge-screened RNA then collapses into a compact intermediate state and subsequently folds into unique native structure with tertiary interactions. Characterization of the folding mechanism under various physiological conditions is an active area of research in order to understand the microscopic mechanisms of RNA folding. Outstanding questions on the folding process include: (1) physical basis of folding nucleation and collapse, (2) the role of cations and RNA sequence in determining the specificity of collapse, (3) the detailed distribution of the structural ensemble, and (4) effect of molecular crowding. In our projects (GUP-21299) we employ the time-resolved and static small angle X-ray scattering (SAXS) at BioCAT to study kinetics and thermodynamics of structural changes of a group I ribozyme from the bacterium Azoarcus. The work includes both wild type and mutants and compares the findings to the more widely studied Tetrahymena intron. The project will provide insight into the nucleation of RNA tertiary structures and make a comparison with theoretical models of electrostatic interactions in unfolded and folded RNAs.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 RNA分子的折叠对于细胞中一系列过程的功能至关重要，包括基因调控，病毒RNA复制和RNA-蛋白质复合物的组装。作为这些过程的一部分，RNA必须折叠成特定的天然结构。RNA的折叠开始于RNA中带负电荷的磷酸基团被阳离子中和。电荷筛选的RNA然后塌陷成紧凑的中间状态，随后折叠成具有三级相互作用的独特天然结构。在各种生理条件下的折叠机制的表征是一个活跃的研究领域，以了解RNA折叠的微观机制。折叠过程中存在的问题包括：（1）折叠成核和折叠的物理基础，（2）阳离子和RNA序列在决定折叠特异性中的作用，（3）结构系综的详细分布，（4）分子拥挤效应。在我们的项目（GUP-21299）中，我们采用时间分辨和静态小角X射线散射（SAXS）在BioCAT研究动力学和热力学的组I核酶的结构变化从细菌Azoarcus。这项工作包括野生型和突变体，并将研究结果与更广泛研究的四膜虫内含子进行了比较。该项目将深入了解RNA三级结构的成核作用，并与未折叠和折叠RNA中静电相互作用的理论模型进行比较。