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RNA protection and decay in yeast mitochondria

酵母线粒体中的RNA保护和衰变

基本信息

批准号：
7900776
负责人：
Carol Louise Dieckmann
金额：
$ 13.84万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-18 至 2011-06-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Mitochondrial function requires the coordinate synthesis of proteins encoded in the nucleus and the organellar genome. The long-term goal of this research is to understand how mitochondrial gene expression is regulated. The focus is on the subset of yeast nuclear genes encoding proteins that enter the organelle to participate in post-transcriptional processes. Each of the seven mitochondrial mRNAs require several message-specific factors that regulate intron removal, mRNA stability and translation. Cbpl has been studied in-depth. It is required specifically for cytochrome b mRNA stability. Recently Cbpl was found to be part of a large multisubunit complex. Cbs2, a factor that specifically promotes translation of COB, is also in a large complex of similar mass. Specific Aim 1 is to analyze the composition and function of these large complexes in RNA protection and translation. Specific Aim 2 is to determine if the two functions of Cbpl, message stabilization and translation, are separable. Specific Aim 3 is to characterize Aep3 in its roles in protection and translation of ATP8/6 mRNA. In addition to the studies on message-specific factors that protect mRNAs and promote their translation, several general factors are important in the turnover of the mRNAs. Overexpression of the Cbt1 protein suppresses mRNA instability, whereas deletion of the CBT1 gene results in defective processing of precursor RNAs. Three other mitochondrial proteins have been implicated in these processing events and mRNA turnover. Cbt1 is in a large complex of proteins of 500,000 daltons. Specific Aim 4 is to analyze the composition and function of this large complex in precursor RNA processing and mRNA turnover. This work will further our general understanding of RNA expression in mitochondria. Many human diseases are caused by mutations in nuclear genes that regulate mitochondrial gene expression. Yeast is a good model system to understand processes that may be affected in human mitochondrial disease syndromes.

描述（由申请人提供）：线粒体功能需要细胞核和细胞器基因组中编码的蛋白质的协调合成。这项研究的长期目标是了解线粒体基因表达是如何调节的。重点是酵母细胞核基因编码的蛋白质，进入细胞器参与转录后过程的子集。七种线粒体mRNA中的每一种都需要几种调节内含子去除、mRNA稳定性和翻译的信息特异性因子。Cbpl已经得到了深入的研究。细胞色素B mRNA稳定性特别需要。最近发现Cbpl是一个大的多亚基复合物的一部分。Cbs 2是一种特异性促进COB翻译的因子，也存在于类似质量的大型复合体中。具体目标1是分析这些大复合物在RNA保护和翻译中的组成和功能。具体目标2是确定Cbpl的两个功能，消息稳定和翻译，是否是可分离的。具体目标3是表征Aep 3在ATP 8/6 mRNA的保护和翻译中的作用。除了对保护mRNA并促进其翻译的信息特异性因子的研究外，几个一般因子在mRNA的周转中也很重要。Cbt 1蛋白的过表达抑制mRNA的不稳定性，而CBT 1基因的缺失导致前体RNA的加工缺陷。其他三种线粒体蛋白质与这些加工事件和mRNA周转有关。cbt 1是一个50万道尔顿的蛋白质大复合体。具体目标4是分析该大复合物在前体RNA加工和mRNA周转中的组成和功能。这项工作将进一步加深我们对线粒体中RNA表达的理解。许多人类疾病是由调节线粒体基因表达的核基因突变引起的。酵母是一个很好的模型系统，以了解可能影响人类线粒体疾病综合征的过程。