Origins and Evolution of tRNA Synthetase Fidelity Modules

University Of Illinois At Urbana-Champaign, Urbana IL

Investigators

Abstract

In every living organism, proteins are faithfully synthesized with high fidelity. A family of enzymes, called the aminoacyl-tRNA synthetases, is responsible for the first step of protein synthesis. In this step specific amino acids are attached to their cognate tRNAs. Some of these enzymes are prone to mistakes (attaching the wrong amino acid to the tRNA) and as a consequence, have developed proofreading and editing mechanisms to reduce mistakes and ensure high fidelity. A high level of accuracy is critical to the proper functioning and viability of each cell. This project will investigate unusual examples of the aminoacyl-tRNA synthetases, which appear to have compromised proofreading and editing mechanisms. One case exists in an ancient archae called Sulfolobus that thrives at high temperatures under acidic conditions typical of hot springs. A different paradigm exists in Mycoplasma, an organism that has undergone genome reduction. This reduced genome has selectively sacrificed the fidelity modules in one of these synthetase enzymes. It is possible that the fidelity mechanisms in these organisms have been compromised in order to provide an innovative pathway to confer a selective advantage. Alternatively, these enzymes might have adapted to rely on novel fidelity mechanisms. The goals of this project have potential to shift existing paradigms about the evolution and fidelity of protein synthesis as well as the maintenance of the genetic code. The project may uncover novel biological mechanisms for cell adaptation and natural selection. Broader Impacts: This project is committed to enhancing scientific literacy of the public via outreach efforts to young children in pre-school and elementary school classrooms. An academic module with an experimental component will introduce students to microbiology and the three kingdoms of life. This module is designed to educate young children in fundamental biology concepts and is expected to broadly impact and stimulate their interest in science. Graduate student training and mentoring will be integrated throughout the research and education plan to enhance professional and scientific development as well as to provide role models to young children as well as undergraduate researchers.