MOLECULAR BASIS OF TRANSLATIONAL FIDELITY

这项拟议的研究涉及到 模式真核生物中的翻译延伸和终止 酿酒酵母。可溶性翻译因素的作用 和其他蛋白质在遗传密码的保真度上进行翻译 作为这部作品的中心主题。突变体影响 将使用延伸率和终止时间来识别和确定 基因和蛋白质在保真过程中的重要作用。 提案的主要重点将放在以下几个方面 真核生物特有的误译，在这种情况下，忠诚被视为一种 决定细胞生长速度的中心参数。为了 提供连续性，翻译保真度的一些特征 原核生物和真核生物共有的细胞器将 也要接受评估。首先，我们建议研究三个翻译 抑制基因，suf12，suf13和suf14，已知或 疑似编码新的保真度蛋白，而这些蛋白似乎没有 功能性原核生物的对应物。对这些基因的研究和 他们的产品将有助于评估这一观点， 分隔的真核细胞可能需要更多的 索菲斯对保真度的控制级别高于 原核生物。提案的第二部分涉及 翻译终止的过程，对于这个过程几乎没有 信息以真核生物的形式提供。终止因素和 终止过程中重要的核糖体成分将是 特色化的。来自这些研究的信息将被用来 对误译和误译之间的评估和明显关系 终止。最后，tRNA的选择和校对 系统将在酵母中研究与两种类型的 误读、氨基酸错误结合和移码。这 工作重点将放在已知的可溶性因子EF-1的功能上 α(负责tRNA与核糖体结合)和EF-2 (负责易位)。关于tRNA的直接信息 在酵母中进行选择和校对将不再需要 对原核系统的间接推断，将有助于评估 真核生物特有的误译现象。

The proposed research is concerned with the fidelity of translational elongation and termination in the model eucaryote Saccharomyces cerevisiae. The role of soluble translation factors and other proteins in the fidelity of genetic code translation will serve as a central theme in this work. Mutants affecting elongation and termination will be used to identify and establish the roles of genes and proteins important in the fidelity process. The major focus of the proposal will be on those aspects of mistanslation unique to eucaryotes in which fidelity is viewed as a central parameter determining cellular growth rate. In order to provide continuity, some features of the translational fidelity apparatus shared in common by procaryotes and eucaryotes will also be assessed. First, we propose to study three translational suppressor genes, suf12, suf13, and suf14, that are known or suspected to encode novel fidelity proteins that appear to have no functional procaryotic counterpart. The study of these genes and their products will aid in assessing the view that complex, compartmentalized eucaryotic cells may require a more sophistocated level of control over fidelity than that required in procaryotes. The second part of the proposal addresses the process of translational termination for which very little information is available in eucaryotes. Termination factors and ribosome components important in the termination process will be characterized. Information from these studies will be used to assess and apparent relationship between mistranslation and termination. Finally, the tRNA selection and proof-reading system will be studied in yeast in relation to two types of misreading, amino acid misincorporation and frameshifting. This work will focus on the function of the known soluble factors EF-1 alpha (responsible for tRNA binding to the ribosome) and EF-2 (responsible for translocation). Direct information on tRNA selection and proof-reading in yeast will obviate the need for indirect inference to procaryotic systems and will help assess aspects of mistranslation unique to eucaryotes.