FUNCTION AND METABOLISM OF RNA

拟议的计划是对人脑的分子生物学的持续分析 核糖核酸酶(RNase)P，一种核糖核蛋白酶，含有 催化RNA参与tRNA加工。本组织的总体目标 项目的目的是了解结构、作用机制和 这种核酶的生物变异。的具体内容 建议的计划包括： 1.继续分析RNaseP的二级和三级结构 系统发育结构比较、化学结构和酶结构 作图、分子内交联和分子动力学计算机 模特儿。 2.继续研究RNaseP RNA-tRNA相互作用 分子间交联、高分辨率化学足迹以及 突变分析。 3.核糖核酸酶P-RNA结构和 机制，侧重于在以下基础上相信的结构元素 之前的结果在反应中是重要的。 4.热稳定的RNase P RNA的继续表征和 基于稳定结构的简化模型核糖核酸酶P RNA的设计 在这些嗜热RNA中识别出的特征。 5.新型真核细胞核糖核酸酶P的特性及其比较 真核细胞核糖核酸酶P-RNA结构分析。 6.古细菌核糖核酸酶P-RNA的连续比较结构分析。 该计划与健康有关，因为它将揭示基本的 RNA功能方面；包括结构、RNA-RNA的性质 相互作用和RNA介导的催化作用。像这样的RNA功能是 对许多病态的病原体来说是基本的，例如病毒 由核糖核酸组成。基于RNA的疗法，例如核酶，提供了 在疾病治疗方面新方向的巨大潜力。RNaseP是 一种杰出的模型，可以帮助我们理解 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.