STRUCTURE/FUNCTION OF YEAST TRANSLATION FACTOR EIF4G

信使RNA（mRNA）上的帽结构和poly（A）尾起作用 一起刺激酵母中的翻译起始， 与翻译起始因子eIF 4G的相互作用。 帽 结合蛋白eIF 4 E和poly（A）尾结合蛋白Pab 1 p介导 eIF 4G与这些mRNA结构的相互作用。 RNA- 活化的ATP酶eIF 4A也与eIF 4G相互作用。 这项建议 概述了实验，其目标是了解这些 蛋白质以及RNA与酵母eIF 4G 1相互作用以及彼此相互作用。 另一个目标是了解eIF 4A的酶活性或 核糖体结合起始因子eIF 3与eIF 4G 1的结合， 当mRNA通过eIF 4 E的相互作用环化时， 和Pab 1 p与eIF 4G 1。 这些实验的最终目标是确定 然后表征其他酵母蛋白， 抑制eIF 4G 1及其相关蛋白的功能。 我们的结果 应该有助于阐明翻译起始的机制， 在真核生物中受到刺激和调节。 此信息将 对理解翻译机制的变化 由某些类型的细胞转化或病毒 感染，并在开发检测方法，然后化合物， 提供治疗选择来纠正这些改变。

The cap structure and the poly(A) tail on messenger RNA (mRNA) work together to stimulate translation initiation in yeast through their interaction with the translation initiation factor eIF4G. The cap binding protein eIF4E and the poly(A) tail binding protein Pab1p mediate the interaction of eIF4G with each of these mRNA structures. The RNA- activated ATPase eIF4A also interacts with eIF4G. This proposal outlines experiments whose goals are to understand how each of these proteins as well as RNA interacts with yeast eIF4G1 and with each other. Another goal is to understand whether eIF4A enzymatic activity or the association of the ribosome bound initiation factor eIF3 with eIF4G1 is stimulated when mRNA is circularized through the interaction of eIF4E and Pab1p with eIF4G1. A final goal of these experiments is to identify and then characterize other yeast proteins which either activate or repress the function of eIF4G1 and its associated proteins. Our results should help to elucidate the mechanisms by which translation initiation is stimulated and regulated in eucaryotes. This information will be invaluable in understanding alterations to the translational apparatus resulting from some types of cellular transformations or viral infections, and in developing assays and then compounds which will provide therapeutic options to correcting these alterations.