Specific Interactions of the Ribosome with the Nascent Peptide

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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.