Discovery of products for probing structure and function of RNase P and human mitochondrial tRNA

Discovery of Products for Probing Structure and Function of RNase P and Human Mitochondrial tRNA
Carol Fierke, Chemistry; David Sherman, Pharmacy; Hashim Al-Hashimi, Chemistry

Ribonuclease P (RNase P) catalyzes the essential 5’ end maturation of tRNA. Nuclear and bacterial RNase P consist 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 while (mt)RNase P is implicated in a number of human diseases. We propose to use screening methods to identify natural products that bind to Bacillus subtilis and mitochondrial RNase P and/or (mt)tRNA using either a fluorescence polarization assay or NMR spectroscopy. 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.