Studies of Translation Initiation in Bacteria

Ohio State University Research Foundation -Do Not Use, Columbus OH

Investigators

Abstract

The final step of gene expression is translation, the synthesis of protein from the information content of messenger RNA (mRNA). Translation occurs in ribosomes, subcellular machines composed of both ribosomal RNA (rRNA) and protein. In recent years, x-ray crystallography and cryo-electron microscopy have revealed the structure of the ribosome and its interactions with a variety of substrates and translation factors. Despite this wealth of structural information, questions of how the ribosome facilitates specific events during translation remain unclear. The goal of this project is to better understand the initiation phase of translation. Initiation is a complex process that requires selection of the initiator tRNA from other species of tRNA and selection of the start codon from other similar or identical triplet sequences in the mRNA. In bacteria, the process is kinetically controlled by initiation factors IF1, IF2 and IF3. In other organisms, initiation is fundamentally similar but more elaborate, involving 10 or more factors in addition to universally conserved IF2 (eIF5B) and IF1 (eIF1A). The Fredrick lab has identified a number of mutations in the rRNA of the small subunit that cause defects in start codon selection. This project is centered on the analysis of these mutations, which will help elucidate the role of rRNA and factors IF1 and IF3 in the initiation process. The broader impact of this project lies in its strong educational emphasis. This project will not only provide research training for both undergraduate and graduate students but will also give research opportunities for secondary educators. Each summer, the laboratory will host a high school science teacher from one of the Columbus Public Schools. While contributing to the research efforts of the laboratory, these teachers will gain experience with modern molecular biology to strengthen their curriculum.