FUNCTION OF THE RO RIBONUCLEOPROTEINS AND THE LA PROTEIN

RO 核糖核蛋白和 LA 蛋白的功能

基本信息

批准号：
2022641
负责人：
Sandra L. Wolin
金额：
$ 10.89万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1993
资助国家：
美国
起止时间：
1993-01-01 至 1998-02-28
项目状态：
已结题

项目摘要

The overall objective of the project is to determine the functions of two conserved cellular components, the Ro ribonucleoprotein particles (RNPs) and the La protein. These two cellular components are frequent targets of the autoimmune response in patients with systemic lupus erythematosus and Sjogren's syndrome. In addition, maternal anti-Ro and anti-La antibodies are highly associated with complete congenital heart block in neonates. The Ro RNPs consist of a 60 kilodalton protein (and possibly additional proteins) that bind one of several small RNA molecules of about 100 nucleotides in length. Although these particles appear to be components of all vertebrate cells, their subcellular location is controversial, and their function is unknown. A subset of the Ro RNPs also binds the La protein, a 50 kd phosphoprotein that binds all known RNA polymerase III transcripts early in their biogenesis. Although the La protein has been suggested to be required for transcription termination by RNA polymerase III, it is possible that this protein functions in some other aspect of the biogenesis of polymerase III RNAs. Like the Ro RNPs, the La protein has been detected in a wide variety of vertebrate cells. In addition, proteins with similar biochemical characteristics as the mammalian La protein have been detected in nematodes and yeast. The ubiquitous distribution and apparent conservation of the Ro RNPs and the La protein argue that they are important components of eukaryotic cells. The first aim of this proposal is to definitively determine the subcellular location of the Ro RNPs using antibodies and nucleic acid probes. The second objective is to identify molecules that interact with Ro RNPs using psoralen and UV-cross-linking and co-immunoprecipitation with anti-Ro antibodies. The third aim is to identify Ro RNPs and the La protein in organisms that will allow a genetic approach to function. The identification of homologues of the Ro RNPs and the La protein in either Drosophila, nematodes or yeast will allow us to assess the consequences of genetically depleting these components from cells and organisms and to genetically identify factors that interact with Ro RNPs and the La protein. Determination of the functions of these conserved cellular components will expand our knowledge of basic cellular processes and may also provide clues to why these particles are frequent targets of the immune response in certain autoimmune diseases.

该项目的总体目的是确定两个功能保守的细胞成分，RO核糖核蛋白颗粒（RNP）和LA蛋白。这两个细胞成分是频繁的目标全身性红斑狼疮患者的自身免疫反应和Sjogren综合征。另外，母体抗罗和抗拉抗体与完全先天性心脏块高度相关新生儿。 RO RNP由60公斤的蛋白质组成（甚至可能其他蛋白质）结合了几个小的RNA分子之一长度约为100个核苷酸。尽管这些粒子似乎是所有脊椎动物细胞的成分，其亚细胞位置为有争议的，它们的功能尚不清楚。 RO RNP的子集还结合了LA蛋白，一种50 kD的磷蛋白，结合了所有已知的 RNA聚合酶III的生物发生早期。虽然已建议LA蛋白转录需要 RNA聚合酶III终止，该蛋白可能在聚合酶III RNA的生物发生的其他方面起作用。像RO RNP一样，LA蛋白已在各种各样的脊椎动物细胞。另外，具有类似生化的蛋白质特征是在哺乳动物LA蛋白中检测到的特征线虫和酵母。无处不在的分布和明显的RORNP和 LA蛋白认为它们是真核的重要组成部分细胞。该提议的第一个目的是确定确定使用抗体和核酸的RO RNP的亚细胞位置探针。第二个目标是确定与之相互作用的分子使用牛cor和紫外线链接和共免疫沉淀的RO RNP 具有抗RO抗体。第三个目的是确定RNP和生物体中的LA蛋白将允许一种遗传方法的功能。识别RO RNP的同源物和LA蛋白果蝇，线虫或酵母都可以使我们能够评估从细胞和生物体并从遗传上识别与RO RNP相互作用的因素和LA蛋白。确定这些保守的功能蜂窝成分将扩大我们对基本蜂窝过程的了解并且还可以提供有关为什么这些粒子是频繁目标的线索某些自身免疫性疾病的免疫反应。