FUNCTION AND METABOLISM OF RNA

拟议的计划是一个持续的分子生物学分析， 核糖核酸酶（RNase）P，一种核糖核蛋白酶，含有 参与tRNA加工的催化RNA。的总体目标 项目是为了了解结构，作用机制和 这种核酶的生物变异。的具体内容 拟议方案是： 1. RNase P二级和三级结构的连续分析， 系统发育结构比较，化学和酶结构 绘图、分子内交联和分子动力学计算机 建模 2.继续研究RNase P RNA-tRNA相互作用， 分子间交联，高分辨率化学足迹，和 突变分析 3. RNase P RNA结构的定向突变检测和 机制，侧重于结构要素， 以前的结果在反应中很重要。 4.热稳定RNase P RNA的连续表征和 基于稳定结构的简化的RNase P RNA模型的设计 在这些嗜热RNA中发现的特征。 5.新型真核RNase P的表征和比较 真核RNase P RNA结构分析。 6.古细菌RNase P RNA的连续比较结构分析。 该计划与健康有关，因为它将阐明基本的 RNA功能的各个方面;包括结构，RNA-RNA的性质 相互作用和RNA介导的催化作用。RNA的这些功能是 是许多病理条件的基本因素，例如病毒 由RNA组成。基于RNA的治疗方法，例如核酶， 在疾病治疗的新方向上具有巨大的潜力。RNase P是 一个杰出的模型，以实现理解的许多方面， RNA功能

The proposed program is a continuing analysis of the molecular biology of ribonuclease (RNase) P, a ribonucleoprotein enzyme that contains a catalytic RNA involved in tRNA processing. The general goals of the project are to understand the structure, mechanism of action and biological variation of this ribozyme. The specific elements of the proposed program are: 1. Continued analysis of RNase P secondary and tertiary structure using phylogenetic structure comparisons, chemical and enzymatic structure mapping, intramolecular crosslinking, and molecular dynamics computer modeling. 2. Continued study of the RNase P RNA-tRNA interaction using intermolecular crosslinking, high-resolution chemical footprinting, and mutational analysis. 3. A directed mutational inspection of RNase P RNA structure and mechanism, focusing on structural elements believed on the basis of previous results to be important in the reaction. 4. Continued characterization of thermally stable RNase P RNAs and the design of a simplified, model RNase P RNA based on stabilizing structural features identified in those thermophilic RNAs. 5. Characterization of novel types of eucaryal RNase P and comparative analysis of eucaryal RNase P RNA structure. 6. Continued comparative structural analysis of archaeal RNase P RNA. The program is health-related in that it will shed light on fundamental aspects of RNA function; including structure, the nature of RNA-RNA interactions, and RNA-mediated catalysis. RNA functions such as these are basic to many agents of pathological conditions, for instance viruses composed of RNA. RNA-based therapeutics, for instance ribozymes, offer enormous potential for new directions in treatment of disease. RNase P is an outstanding model for achieving an understanding of the many facets of RNA function.