Structure-selective RNA Cleavage by Metal Ion Catalysts

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This research award in the Inorganic, Bioinorganic and Organometallic Chemistry program supports work by Professor Janet Morrow at the University at Buffalo, State University of New York, to examine the structure-selective cleavage of RNA by mononuclear and dinuclear metal ion catalysts with the goal of developing catalysts for RNA structure mapping and developing small molecules for specific interaction with common secondary structures of nucleic acids. First, mononuclear and dinuclear complexes of scandium(III) and lanthanides(III) will be prepared and studied as structure-selective RNA cleavage catalysts. Second, recognition agents that bind to uridine or thymidine containing bulges, mismatches or loops in RNA or DNA, respectively, will be developed. These recognition agents are based on zinc(II) macrocyclic complexes with attached pendent aromatic groups. Third, zinc(II) complex binders will be tethered to scandium(III) or europium(III) catalysts and the structure-selective cleavage of RNAs containing uridines in bulges and loops will be studied. Lanthanide ion complexes and their interactions with nucleic acids will be characterized by using luminescence spectroscopy. In addition to training graduate and undergraduate students in multidisciplinary research, research training will be extended to undergraduate courses by the creation of a new laboratory module for our CASPiE program (Center for Authentic Practice in Education). This module will involve studies to monitor binding of small molecules to DNA. The Morrow group will develop and maintain a specialized laser system for the direct excitation of lanthanide luminescence and keep the facility open to all researchers. This includes students and faculty members from the State University of New York at Fredonia for our collaborative work on the study of metal ion complex binding to nucleic acids. This work will provide new tools for the study of RNA protein interactions and RNA structure in vitro and in cell culture and will be a first step towards targeting specific RNA structures to control biological function.