STRUCTURE AND FUNCTION OF RIBONUCLEASE P IN ARCHAEA

拟议的计划是对RNA的结构和功能的研究 古生代核糖核酸酶P组分(又名古细菌)。独一无二的 古生菌RNaseP酶的特征是它们的RNA亚基是 尽管它们很相似，但它们本身不能在体外催化 按其催化熟练的细菌同系物的顺序排列。这个 拟议计划的主旨是加深对 古生菌和细菌核糖核酸酶P酶的结构差异和 这些相似之处和不同之处如何促成功能(或不足 其中)的核酶。该计划的具体内容包括： L。古生代核糖核酸酶PRNA结构的分析(次要的是什么 和三级结构的古生菌核糖核酸酶P RNA以及它与 它是催化熟练的细菌同系物？) 2.古生菌核糖核酸酶P-RNA的结构基础分析 细菌核糖核酸酶P RNA与古细菌核糖核酸酶P RNA的缺陷(S) 对生化缺陷负有责任吗？) 3.古生菌核糖核酸酶P-RNA的生化性质分析 缺陷(催化循环的哪一步(S)可以和不能通过 古生菌RNaseP RNA？) 4.确定和表征该物质的附加成分 古生菌核糖核酸酶P全酶(有哪些其他成分 精通催化的全酶及其对 结构和/或催化？)。 5.在核糖体RNA中寻找新的催化RNA 加工途径。 拟议的计划与健康有关，因为它将提供 RNA催化的基本方面，它们之间的关系 RNA的结构和功能，以及与RNA相互作用的性质 其他大分子。这方面的知识对于理解 由RNA介导的病理，如RNA病毒感染和癌基因 表情。以RNA为基础的试剂，特别是催化RNA，如RNaseP， 显然将是基因治疗的一个重要方面 各种疾病。古核糖核酸酶P‘s，因为依赖于 它们的RNA对其他附加因子的功能，提供了重要的 核糖核酸酶P-RNA结构基本成分检测系统 和功能。

The proposed program is a study of the structure and function of the RNA component of ribonuclease P in Archaea (a.k.a. archaebacteria). The unique characteristic of archaeal RNase P enzymes are that their RNA subunits are not by themselves capable of catalysis in vitro despite their resemblance in sequence to their catalytically-proficient bacterial homologs. The thrust of the proposed program is to develop an understanding of the structural differences between archaeal and bacterial RNase P enzymes and how these similarities and differences contribute to the function (or lack thereof) of the ribozyme. The specific elements of this program are: l. The analysis of archaeal RNase P RNA structure (What is the secondary and tertiary structure of archaeal RNase P RNA and how does it compare to it's catalytically-proficient bacterial homolog?). 2. The analysis of the structural basis of the archaeal RNase P RNA's defect (What difference(s) between the bacterial and archaeal RNase P RNAs are responsible for the biochemical defect?). 3. The analysis of the biochemical nature of the archaeal RNase P RNA's defect (What step(s) of the catalytic cycle can and cannot be performed by archaeal RNase P RNA?). 4. The identification and characterization of additional components of the archaeal RNase P holoenzyme (What are the other components of the catalytically-proficient holoenzyme and how do they contribute to structure and/or catalysis?). 5. A preliminary search for novel catalytic RNAs in the ribosomal RNA processing pathway. The proposed program is health-related because it will provide insight into basic aspects of catalysis by RNA, the relationships between structure and function in RNA, and the nature of interactions of RNA with other macromolecules. This knowledge is essential for the understanding of pathologies mediated by RNAs, such as RNA virus infection and oncogene expression. RNA-based agents, especially catalytic RNAs such as RNase P, will clearly be an important facet of gene-therapy treatments for a variety of diseases. Archaeal RNase P's, because of the dependence of their RNAs on other additional factors for function, provide an important system for the examination of essential elements of RNase P RNA structure and function.