MRNA DEGRADATION AND TRANSLATION CONTROL IN YEAST

描述（改编自申请人摘要）：总体目标 这个建议是为了了解转录物降解途径， 其与翻译控制的关系，使用芽殖酵母S. 酿酒酵母作为模型系统。重点是XRN 1基因，编码 酵母的主要5 '-3'核糖核酸外切酶活性，并被认为是 RNA周转途径后期的主要分解代谢酶。 研究人员打算通过以下方法鉴定途径中的其他基因： 用XRN等位基因筛选合成致死突变 (Aim 1）并表征所获得的突变体（包括已经 已知的SKI 2基因）在体内RNA周转和翻译中的作用（Aim 2）， 体外（目标4）。目的3涉及XRN 1的靶向诱变， 分析其功能结构域并获得显性负突变。 许多参与RNA周转和翻译控制的蛋白质出现 在真核生物中高度保守，被认为有助于细胞 应对病原性感染和肿瘤发生等挑战。

DESCRIPTION (Adapted from applicant's abstract): The overall goal of this proposal is to understand the transcript degradation pathway and its relationship to translational control, using the budding yeast S. cerevisiae as a model system. The focus is on the XRN1 gene, encoding the major 5'-3' exoribonuclease activity of yeast and believed to be the major catabolic enzyme in the late stages of the RNA turnover pathway. The investigator intends to identify other genes in the pathway by screening for mutations that are synthetically lethal with xrn alleles (Aim 1) and to characterize the mutants obtained (including the already known SKI2 gene) in RNA turnover and translation, in vivo (Aim 2) and in vitro (Aim 4). Aim 3 is directed at targeted mutagenesis of XRN1 to analyze its functional domains and obtain dominant negative mutations. Many proteins involved in RNA turnover and translation control appear highly conserved among eukaryotes and are thought to help the cell respond to such challenges as pathogenic infection and oncogenesis.