Regulators of Translation Elongation Factor 1 Alpha

描述(由申请人提供)： 基因表达的调控对细胞的生长发育至关重要。调节基因表达的转录和转录后机制的成功取决于功能多肽的成功合成。许多可溶性翻译因子、氨基酰tRNAs(AA-tRNAs)和核糖体相互作用，产生细胞所需的新生多肽链。这项建议使用翻译延长因子eEFIA作为中心点，从这个中心点来检查翻译机制的这些关键组件之间的相互作用，这些组件的功能确保准确和适当的蛋白质合成。对eEF1A功能的分析将剖析确保翻译保真度的机制，以及eEF1A如何整合AA-tRNA和核糖体之间的通讯。作为一种G蛋白，对eEF1a的研究对我们理解细胞通过核苷酸交换和水解的调控机制具有重要意义。酿酒酵母允许采用遗传和生物化学相结合的方法来解决有关伸长机制和保持翻译准确性的关键问题。虽然这些研究对所有真核系统都有影响，但eEF1A与真菌特异性翻译因子eEF3的相互作用定义了真菌特有的过程。EEF3与eEF1a和核糖体的相互作用及其在体内的基本功能，支持了eEF3在真菌蛋白质合成中的关键作用。EEF3在翻译准确性中的作用也被提出，然而，关于eEF3对体内保真度的影响知之甚少。准确的蛋白质合成是确保现有的调节基因表达的调节机制有效的关键一步。有趣的是，翻译延长的准确性是许多病毒为了完成其生命周期的关键部分而操纵的过程。拟议的研究解决了确保真核生物翻译准确性所涉及的关键沟通问题，同时可能对病毒与宿主的相互作用产生新的见解。此外，对真菌特异性翻译因子的分析增强了我们对蛋白质合成的一个独特方面的理解，并可能产生新的抗真菌靶点。

DESCRIPTION (provided by applicant): The regulation of gene expression is critical for cell growth and development. The success of transcriptional and post-transcriptional mechanisms that regulate gene expression hinge upon the successful synthesis of functional polypeptides. Many soluble translation factors, the aminoacyltRNAs (aa-tRNAs) and the ribosome interact to produce nascent polypeptides chains required by the cell. This proposal uses the translation Elongation Factor eEFIA as a central point from which to examine the interactions between these critical components of the translation machinery that function to ensure accurate and appropriate protein synthesis. The analysis of eEF1A function will dissect the mechanisms by which translational fidelity is ensured and how eEF1A serves to integrate the communication between the aa-tRNA and the ribosome. As a G-protein, work on eEF1A has implications in our understanding of cellular regulatory mechanism through nucleotide exchange and hydrolysis. The yeast Saccharomyces cerevisiae allows a combined genetic and biochemical approach to address key questions regarding the mechanism of elongation and the maintenance of translational accuracy. While these studies have implications for all eukaryotic systems, the interaction of eEF1A with the fungal specific translation factor eEF3 defines a process unique to fungi. The interaction of eEF3 with eEF1A and the ribosome, and its essential function in vivo, support the role of eEF3 as a key player in fungal protein synthesis. Roles for eEF3 in translational accuracy have also been proposed, however, little is known about the effects of eEF3 on fidelity in vivo. Accurate protein synthesis is a critical step in ensuring the regulatory mechanisms that exist for modulating gene expression are productive. Interestingly, the accuracy of translation elongation is a process many viruses manipulate to complete a critical part of their life cycle. The proposed studies address the critical communication involved in ensuring translational accuracy in eukaryotes, while potentially yielding new insights into viral-host interactions. Additionally, the analysis of a fungal specific translation factor enhances our understanding of a unique aspect of protein synthesis and may yield new anti-fungal targets.