Discovery of Natural Products for Probing the Structure and Function of tRNA Processing
Ribonuclease P (RNase P) catalyzes the essential 5’ end maturation of tRNA. Nuclear and bacterial RNase P consists of a single catalytic RNA subunit and variable numbers of protein subunits while human mitochondrial RNase P is composed solely of protein. Bacterial RNase P is an attractive potential antibacterial target. To date, no specific RNase P inhibitor has been identified. We propose to use screening methods to identify natural products that bind to Bacillus subtilis and mitochondrial RNase P and (mt)tRNA using either a fluorescence polarization assay or NMR spectroscopy in collaboration with Professor David Sherman and Hashim Al-Hashimi. We will then evaluate the functional effects of these ligands on growth and tRNA processing. Finally, we will investigate (mt)tRNA structure and dynamics using NMR spectroscopy. These studies will significantly enhance our understanding of the structure and function of bacterial RNase P, human (mt)tRNA and mtRNase P.