Speaker: Victoria DeRose (University of Oregon)
Recognition of the diverse biological roles played by RNA is continually growing. In particular, it is increasingly apparent that a vast underworld of non-coding RNA regulates cellular function. RNA function is often tied to its ability to form complex structures and, due to its polyanionic nature, RNA structure depends strongly on cations. In some cases, metal ions are captured in specific and critical sites. Two areas of metal-RNA interactions that are of particular interest are the catalytic centers of ribozymes, and RNA targeting by metal-based therapeutics. In the Hammerhead ribozyme, we have pursued spectroscopic and functional studies that probe the influence of active-site metal ions on phosphodiester bond cleavage reactions that are catalyzed by this RNA. These and other RNA sites also capture metallo-drugs such as the anticancer compound cisplatin. Using S. cerevisiae as a model system, we find evidence for extensive in vivo RNA-Pt(II) adduct formation and specific targeting of the ribosome and other cellular RNAs. Downstream consequences of cellular RNA-drug interactions are under investigation.