RNA FOLDING STRUCTURE AND KINETICS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 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-蛋白质的组装 复合体。作为这些过程的一部分，RNA必须折叠成特定的天然结构。 RNA的折叠始于带负电荷的磷酸基团的中和 通过阳离子在RNA中。然后，电荷筛选的RNA坍塌成致密的中间体 状态，然后折叠成具有三级相互作用的独特的自然结构。 折叠途径的特征是一个活跃的研究领域，以了解 RNA折叠的微观机制。关于折叠的悬而未决的问题 过程包括：(1)折叠成核和崩塌的动力学细节，(2)作用 阳离子和RNA序列在决定塌陷特异性中的作用，以及(3) 结构整体的详细分布。在我们的工作中，我们使用了时间分辨的 和静态小角X射线散射(SAXS)在BioCAT研究动力学和 细菌I类核酶结构变化的热力学研究 阿佐阿科斯。这项工作包括野生型和突变型，并将发现与 研究较广泛的四膜虫内含子。该项目将提供对 核糖核酸三级结构的成核作用及其与理论模型的比较 未折叠和折叠RNA中的静电相互作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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 compact intermediate state and subsequently folds into unique native structure with tertiary interactions. Characterization of folding pathway is an active area of research in order to understand the microscopic mechanisms of RNA folding. Outstanding questions on the folding process include: (1) details of the kinetics of folding nucleation and collapse, (2) the role of cations and RNA sequence in determining the specificity of collapse, and (3) the detailed distribution of the structural ensemble. In our work 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.