RNA FOLDING STRUCTURE AND KINETICS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级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-蛋白质复合体的组装。作为这些过程的一部分，RNA必须折叠成特定的天然结构。RNA的折叠始于阳离子中和RNA中带负电荷的磷酸基团。然后，电荷筛选的RNA塌陷成致密的中间状态，随后折叠成具有三级相互作用的独特自然结构。为了理解RNA折叠的微观机制，表征各种生理条件下的折叠机制是一个活跃的研究领域。关于折叠过程的突出问题包括：(1)折叠成核和折叠的物理基础，(2)阳离子和RNA序列在决定折叠的特异性中的作用，(3)结构系综的详细分布，以及(4)分子拥挤效应。在我们的项目(GUP-21299)中，我们使用BioCAT的时间分辨和静态小角X射线散射(SAXS)来研究固氮弧菌I组核酶结构变化的动力学和热力学。这项工作包括野生型和突变型，并将发现与更广泛研究的四膜虫内含子进行比较。该项目将提供对RNA三级结构成核的洞察，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。

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.