Composition and Function of Mitochondrial RNPs

线粒体 RNP 的组成和功能

• 批准号: 7252564
• 负责人: SERAFIN PINOL-ROMA
• 金额: $ 22.81万
• 依托单位: CITY COLLEGE OF NEW YORK
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7252564
• 关键词: Address; Affect; Agreement; Antisense RNA; Binding; Biochemical; Cell Nucleus; Cells; Coenzyme A; Complex; Cytochrome-c Oxidase Deficiency; Cytosol; DNA; Defect; Disease; Dominant-Negative Mutation; Eukaryota; Eukaryotic Cell; Event; Gene Expression; Genes; Genetic Transcription; Human; Indium; Knowledge; Life; Messenger RNA; Metabolic; Metabolism; Mitochondria; Mitochondrial DNA; Mitochondrial Proteins; Mitochondrial RNA; Mutation; Nuclear; Numbers; Oxidoreductase; Personal Satisfaction; Process; Production; Property; Proteins; RNA; RNA Binding; RNA Interference; RNA Processing; RNA Recognition Motif; Regulation; Research; Research Personnel; Respiration; Role; Site; Testing; Trans-Activators; Transcript; Translating; Vertebrates; Work; crosslink; in vivo; insight; mitochondrial genome; novel; protein crosslink; ultraviolet irradiation

DESCRIPTION (provided by applicant): Mitochondria are the main sites of cellular energy production in eukaryotes. Most mitochondrial proteins are encoded by nuclear genes, translated in the cytosol, and subsequently imported into mitochondria, while a few are encoded by mitochondrial DNA (mtDNA). Thus, mitochondrial function is controlled by both nuclear and mitochondrial genomes. In humans, mtDNA encodes 13 of the proteins involved in respiration. The mRNAs for these proteins are derived by processing of polycistronic primary transcripts that also contain mt rRNAs and tRNAs. The importance of mitochondrial gene expression to human well-being is underscored by the growing number of diseases that are being found to result from defects in mitochondrial gene expression in general, and from mitochondrial RNA processing in particular. Very little is known about the trans-acting factors that participate in this processing and in the subsequent function of the RNA. In order to understand in detail mitochondrial gene expression and its regulation in vertebrates, many fundamental questions still need to be addressed regarding the factors involved in mitochondrial RNA metabolism, beginning with studying in detail their identity and fundamental properties. The research proposed here aims at filling this gap by studying in detail the proteins that associate with mitochondrial RNA. The proposed work uses as a starting point the characterization of LRP130, which was recently identified as the most prominent protein among those that are crosslinked to mitochondria by UV irradiation of living cells. Mutations in LRP130 were recently found to cause (mitochondrial) cytochrome c oxidase deficiency in humans, in agreement with a potential direct role of LRP130 in mitochondrial RNA metabolism. Significantly, LRP130 has no recognizable RNA-binding domains. Our hypothesis is that LRP130 binds mRNA through a novel type of RNA-binding domain, that it is a major component of mitochondrial RNP complexes, and that it participates in the metabolism of mitochondrial RNA. This hypothesis will be tested by characterizing the RNA-binding activity of LRP130 and its associated proteins, by delineating in detail the composition of mitochondrial RNA-protein complexes in which LRP130 is found, and by beginning to investigate the function of LRP130 and its associated proteins in mitochondrial gene expression.

描述（由申请人提供）： 线粒体是真核生物中细胞能量产生的主要部位。大多数线粒体蛋白由核基因编码，在细胞质中翻译，然后进口到线粒体中，而其中一些则由线粒体DNA（mtDNA）编码。因此，线粒体功能由核和线粒体基因组控制。在人类中，mtDNA编码涉及呼吸的13个蛋白质。这些蛋白质的mRNA是通过处理也包含MT rRNA和TRNA的多用途主要转录物来得出的。线粒体基因表达对人类福祉的重要性突显了越来越多的疾病，这些疾病是由于一般的线粒体基因表达缺陷而引起的，特别是由于线粒体RNA的处理，尤其是由于线粒体RNA的处理。关于参与该处理以及RNA随后功能的跨性别因子知之甚少。为了详细了解线粒体基因的表达及其在脊椎动物中的调节，关于线粒体RNA代谢所涉及的因素仍然需要解决许多基本问题，从详细研究其身份和基本特性开始。这里提出的研究旨在通过详细研究与线粒体RNA相关的蛋白质来填补这一空白。拟议的工作用作LRP130的表征的起点，LRP130的表征最近被确定为通过活细胞的UV辐照到线粒体的那些最突出的蛋白质。最近发现LRP130中的突变会导致（线粒体）细胞色素C氧化酶缺乏，与LRP130在线粒体RNA代谢中的潜在直接作用一致。值得注意的是，LRP130没有可识别的RNA结合域。我们的假设是LRP130通过一种新型的RNA结合结构域结合mRNA，它是线粒体RNP复合物的主要组成部分，并且参与线粒体RNA的代谢。通过表征LRP130及其相关蛋白的RNA结合活性，通过详细介绍线粒体RNA-蛋白质复合物的组成，在其中发现LRP130，并开始研究LRP130及其相关蛋白在线粒体基因表达中的功能。