“Impact of Modified Nucleosides on rRNA Structure and Ligand Binding”

Post-transcriptional modifications play important roles in modulating the functions of RNA. The presence of modifications may directly alter interactions with binding partners or cause structural changes that indirectly affect ligand recognition. Among the RNA species, ribosomal RNAs (rRNAs) provide numerous examples of modification types located in differing sequence and structural contexts. These RNAs often display conservation in sequence, secondary structure, tertiary interactions, and modifications, also trademarks of ideal drug-targeting sites. Ligand interactions with these regions favor certain modification-induced RNA conformational states. Our laboratory uses a combination of synthesis and biophysical methods to study the rRNA modifications in motifs such as helix 69 (H69) of the large subunit rRNA. Taking advantage of the structural diversity offered by specific modifications, phage display was used to select peptides that bind to H69. Our results indicate roles for pseudouridine in mediating ligand interactions with H69.

Professor Christine Chow, Dept. of Chemistry, Wayne State University