MECHANISM AND KINETICS OF RNA FOLDING BY SAXS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 理解RNA的折叠机制对于理解基因调控、病毒RNA复制和RNA-蛋白质复合物组装等生物过程至关重要。RNA的折叠是由阳离子中和磷酸盐电荷驱动的。在阳离子的存在下，RNA折叠成天然的三级结构，然后最初折叠成紧凑的中间体。据信，不同的折叠途径划分RNA群体，其中一些在动力学上被捕获在错误折叠的中间体中。然而，RNA折叠机制的细节仍不清楚，包括以下重要问题：（1）折叠成核和折叠的动力学机制，（2）阳离子和RNA序列在确定折叠特异性中的作用，以及（3）结构系综的宽度。为了解决这些问题，我们正在BioCAT上使用时间分辨和静态小角X射线散射（SAXS）对来自细菌Azoarcus的I组核酶进行分析。结果将深入了解RNA折叠的早期阶段，并提供实验测试的理论模型的静电相互作用在未折叠和折叠的RNA。

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. Understanding the folding mechanism of RNA is crucial for understanding biological processes such as gene regulation, viral RNA replication, and the assembly of RNA-protein complexes. Folding of RNAs is driven by neutralization of phosphate charge by cations. In the presence of the cations, RNAs fold into native tertiary structure following an initial collapse into compact intermediates. It is believed that different folding pathways partition the RNA population, some of which is kinetically trapped in misfolded intermediates. However, the details of the RNA folding mechanisms remain unclear, including the following important questions: (1) the kinetic mechanism of folding nucleation and collapse, (2) the role of cations and RNA sequence in determining specificity of collapse, and (3) the breadth of the structural ensemble. In order to address these questions, we are using time-resolved and static small angle X-ray scattering (SAXS) at BioCAT on a group I ribozyme from the bacterium Azoarcus. The results will give insight into the early stages of RNA folding and provide experimental tests of theoretical models of electrostatic interactions in unfolded and folded RNAs.