Specific Interactions of the Ribosome with the Nascent Peptide

基因表达的调控对细胞存活至关重要。基因表达如何受到核糖体机制的影响，核糖体机制将基因翻译成蛋白质，这一点仍然知之甚少。当前提案的目标是了解遗传编程翻译效应如何控制细菌中的基因表达。这些发现预计将显着扩大核糖体在控制基因表达中的作用及其作为小分子传感器的功能的知识，并提供对变化环境的细胞反应的见解。这些知识将提高我们对基因调控和蛋白质合成基本原理的理解，并可能为控制基因表达开辟新的途径。该项目还将有助于丰富PI和Co-PI教授的药学专业和研究生的课程，提供扩大高中生培训的机会，并提高他们对STEM学科的兴趣。此外，该项目将使研究生能够参与外联活动，例如帮助在少数民族学生人数较多的市中心学校组织科学博览会，参加芝加哥比尔森社区真正价值男孩和女孩俱乐部的科学俱乐部，该社区主要是西班牙裔人口，或在扩展您的视野（EYH）内举办研讨会网络，有助于暴露中学女生干活动和职业。有越来越多的赞赏的潜力，核糖体及其相互作用，新生多肽在基因表达中起关键作用。然而，新生肽识别核糖体的分子机制，翻译事件的频谱，可以调整新生蛋白质，和新生肽基因调控的程度仍然知之甚少。该提案的一个目标是在分子水平上了解控制细菌铜离子转运蛋白基因表达的程序化移码操作，特别强调信使RNA中编码的刺激元件的作用，最重要的是，在新生肽中。第二个目标是获得对缓慢终止现象的基本见解，这种现象在细菌基因组中普遍存在，但只影响特定的基因子集。基因组规模和生物化学方法，特别是最近开发的创新Ribo-T系统，将用于推进这些目标。该项目由生物科学理事会分子和细胞生物科学司的遗传机制集群和工程理事会化学、生物工程、环境和运输系统司的生物技术和生物化学工程项目共同资助。

Regulation of gene expression is critical for cell survival. How gene expression is affected by the functioning of the ribosome machinery that translates genes into proteins remains poorly understood. The goals of the current proposal are to understand how genetically programmed translation effects control gene expression in bacteria. The findings are anticipated to significantly expand knowledge of the role of the ribosome in controlling gene expression and its functions as a small molecule sensor, and provide insights into cellular responses to changing environments. This knowledge will improve our understanding of fundamental principles of gene regulation and protein synthesis, and potentially open new avenues for controlling gene expression. The project will also help enrich the curriculum for Pharmacy professional and graduate students taught by PI and Co-PI, provide opportunities to expand training of high school students and increasing their interest in STEM disciplines. Additionally, the project will enable involvement of graduate students in outreach activities such as helping organize science fairs in inner-city schools with large minority student populations, participating in the Science Club of the True Value Boys and Girls Club in the Pilsen neighborhood of Chicago, which has a largely Hispanic population, or running workshops within the Expanding Your Horizons (EYH) network that helps to expose middle school girls to STEM activities and careers.There is growing appreciation of the potential of the ribosome and its interactions with the nascent polypeptide to play a critical role in gene expression. However, the molecular mechanisms of nascent peptide recognition by the ribosome, the spectrum of translation events that may be tuned by the nascent protein, and the extent of gene regulation by nascent peptides remain poorly understood. One goal of the proposal is to understand, at the molecular level, the operation of programmed frameshifting that controls expression of a bacterial copper ion transporter gene, with special emphasis on the role of stimulatory elements encoded in the messenger RNA and, most importantly, in the nascent peptide. The second goal is to gain fundamental insights into the phenomenon of slow termination, which is prevalent in the bacterial genomes but affects only a specific subset of genes. Genome scale and biochemical approaches, especially involving the recently developed innovative Ribo-T system, will be used to advance these goals.This project is funded jointly by the Genetic Mechanisms Cluster in the Division of Molecular and Cellular Biosciences, Directorate for Biological Sciences, and the Biotechnology and Biochemical Engineering Program in the Division of Chemical, Bioengineering, Environmental and Transport Systems, Directorate for Engineering.