RNA protection and decay in yeast mitochondria

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编码蛋白质的协调合成。这项研究的长期目标是了解线粒体基因表达是如何被调节的。重点是酵母核基因的子集编码蛋白质进入细胞器参与转录后的过程。这七种线粒体mRNA中的每一种都需要一些信息特异性因子来调节内含子的去除、mRNA的稳定性和翻译。Cbpl已被深入研究。它是细胞色素b mRNA稳定性所必需的。最近发现Cbpl是一个大的多亚基复合体的一部分。Cbs2是一个专门促进COB翻译的因子，也在一个类似质量的大复合体中。具体目的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，是否可分离。特异性目的3是表征Aep3在保护和翻译ATP8/6 mRNA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，一些一般因子在mrna的周转中也很重要。Cbt1蛋白的过表达会抑制mRNA的不稳定性，而Cbt1基因的缺失会导致前体rna的加工缺陷。另外三种线粒体蛋白与这些加工事件和mRNA转换有关。Cbt1存在于一个50万道尔顿的大型蛋白质复合体中。具体目的4是分析这个大复合体在前体RNA加工和mRNA转换中的组成和功能。这项工作将进一步加深我们对线粒体中RNA表达的一般理解。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来了解可能影响人类线粒体疾病综合征的过程。

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.