Towards solution of the RNA folding problem

致力于解决RNA折叠问题

基本信息

批准号：
8233539
负责人：
Michael D. Brenowitz
金额：
$ 33.76万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-05-01 至 2015-02-28
项目状态：
已结题

项目摘要

Project Summary RNA molecules often must fold into distinct three-dimensional structures to exert their biological function. These folded structures may be large or small, long-lived or transient, and/or stable or unstable in nature. The kinetics of RNA folding is characterized by multiple pathways, the population of intermediates and often (but not always) on- and/or off-pathway kinetically trapped species. Our approach to understanding how the RNA is folded is to determine which folding pathways are possible in vitro with the goal of determining the subset that occur in vivo. We computationally integrate local and global measures of folding into `structural-kinetic' models that characterize folding reactions from their earliest steps. Our development of high-throughput methods for the acquisition of time progress curves with millisecond time and single nucleotide spatial resolution allows general hypotheses to be tested against experimental data that is both deep and broad. The proposed studies of group I introns seek to establish quantitative relationships between RNA structure, stability and folding kinetics by critically comparing the folding of phylogenetically related RNA molecules and gentle systematic perturbation of tertiary contacts. The folding of a riboswitch whose structure is homologous to the catalytic core of group I intron is analyzed to determine if these different regulatory elements possess a common folding mechanism. We explore the effect on the observed emergent folding behavior solution variables such as temperature and ionic conditions that affect the microscopic environment of RNA in order to understand the relationships between the physical environment and folding environment. Lastly, we seek to understand how transcription affects RNA folding.

项目概要 RNA 分子通常必须折叠成不同的三维结构才能发挥其生物作用功能。这些折叠结构可以大或小、寿命长或短暂、和/或稳定或稳定。性质不稳定。 RNA 折叠动力学的特点是多途径、群体中间体和经常（但不总是）在路径上和/或路径外动力学捕获的物种。我们的了解 RNA 如何折叠的方法是确定哪些折叠途径是可能的体外实验，目的是确定体内发生的子集。我们通过计算整合本地以及折叠成“结构动力学”模型的全局测量，这些模型表征了折叠反应他们最早的脚步。我们开发用于获取时间进度的高通量方法具有毫秒时间和单核苷酸空间分辨率的曲线允许一般假设根据既深入又广泛的实验数据进行了测试。 I组内含子的拟议研究寻求建立 RNA 结构、稳定性和折叠动力学之间的定量关系批判性地比较系统发育相关的 RNA 分子的折叠和温和的系统三级接触的扰动。结构与核糖开关同源的核糖开关的折叠分析 I 组内含子的催化核心以确定这些不同的调控元件是否具有一种常见的折叠机构。我们探讨了对观察到的紧急折叠行为的影响影响微观环境的溶液变量，例如温度和离子条件 RNA以了解物理环境和折叠之间的关系环境。最后，我们试图了解转录如何影响 RNA 折叠。