Understanding of ribosome function has been a goal of molecular biology for more than 50 years. Of particular interest has been the mechanism by which the ribosome achieves translational accuracy, and how accuracy is perturbed by highly effective antibiotics. Rules for how ribosome distinguishes correct and incorrect decoding events have been developed. The work proposed here seeks a broader understanding at this level using a novel approach. A unique RNA molecule, tmRNA , and its intreraction with the ribosome will be examined. TmRNA has features of both a tRNA and an mRNA and functions to terminate translation of stalled ribosomes. In order to carry out its function in the ribosomal A site, a tmRNA is proposed to mimic the codon-anticodon interaction of the normal tRNA mRNA interaction. The proposed research will utilize a sensitive genetic screen to identify tmRNA mutants that have reduced or increased function in vivo, characterize those mutants at the molecular level to identify determinants recognized by the ribosome, and examine promising candidates, genetically and with key antibiotics to determine if they are defective in responding to the rules for accurate decoding by the ribosome. A deeper understanding of these processes will not only reveal new functional aspects of both the tmRNA and the ribosome but likely yield new insights into how antibiotics function and how new antibiotics might be discovered.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31GM066363-02
Application #
6608916
Study Section
Special Emphasis Panel (ZRG1-F05 (29))
Program Officer
Toliver, Adolphus
Project Start
2002-08-01
Project End
Budget Start
2003-08-01
Budget End
2004-07-31
Support Year
2
Fiscal Year
2003
Total Cost
$26,648
Indirect Cost
Name
University of California Los Angeles
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Maar, Dianna; Liveris, Dionysios; Sussman, Jacqueline K et al. (2008) A single mutation in the IF3 N-terminal domain perturbs the fidelity of translation initiation at three levels. J Mol Biol 383:937-44