MOLECULAR BASIS OF TRANSLATIONAL FIDELITY

拟议的研究涉及的保真度 模式真核生物中的翻译延伸和终止 酿酒酵母 可溶性翻译因子的作用 和其他蛋白质在遗传密码翻译的保真度将 是这部作品的中心主题 突变体影响 延伸和终止将用于识别和建立 基因和蛋白质在保真度过程中的重要作用。 建议的主要重点将放在以下方面： 真核生物特有的误译，其中保真度被视为 决定细胞生长速率的中心参数。 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器官将 也要评估。 首先，我们研究了三种翻译方法。 抑制基因suf 12、suf 13和suf 14，已知或 怀疑编码新的保真度蛋白，似乎没有 功能性原核对应物。 对这些基因的研究， 他们的产品将有助于评估复杂的， 分隔的真核细胞可能需要更多的 对保真度控制水平比 原核生物 建议的第二部分涉及 翻译终止的过程， 在真核生物中可获得信息。 终止因素和 在终止过程中重要的核糖体成分将被 表征了 这些研究的信息将用于 误译与翻译的关系 终止 最后是tRNA的选择和校对 系统将在酵母中研究两种类型的 误读、氨基酸错误掺入和移码。 这 工作将集中在已知的可溶性因子EF-1的功能上 α（负责tRNA与核糖体的结合）和EF-2 （负责易位）。 关于tRNA的直接信息 酵母中的选择和校对将满足 间接推断原核系统，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.