This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5). Intellectual Merit: The long-range objective of this project is to achieve a more fundamental understanding of how functional RNA (ribonucleic acid) molecules perform their biological activities, and the role of metal ions in these processes. Whereas the sole biological role of DNA (deoxyribonucleic acid) is to encode a cell's genetic information, the biochemical properties of RNA, its chemical cousin, enable it to mediate critical roles in numerous steps in gene expression, including regulation and catalysis. The power of RNA to perform its wide range of activities stems both from chemical differences (specifically, an oxygen atom missing from the sugar component of DNA) and from the ability of single-stranded RNA to fold into myriad conformations, each capable of a specific function. An additional feature of functional RNA molecules is the ability to bind certain metal ions in specific locations, which extend the structural and catalytic properties of the folded RNA. The aims of this research are to examine the metal ion binding properties of the small nuclear (sn)RNA molecules that, together with numerous proteins, form the spliceosome. The eukaryotic spliceosome mediates a pivotal activity that removes noncoding regions from precursor messenger (pre-m)RNA molecules prior to their translation into protein. Specific interaction with metal ions by snRNAs is essential for spliceosome assembly and catalytic activity, yet little is known about the detailed structure of individual binding sites and the role of these metal ions in catalytic activity. The significance of this research lies in its potential to achieve a more detailed understanding of the interrelationship between structural and chemical properties of RNA-metal ion complexes. These data will greatly enhance fundamental understanding of the processes involved in RNA-mediated catalysis and will generate new methods. The broader impact of this work includes: 1) education of graduate and undergraduate students in a laboratory that provides them with interdisciplinary training in molecular biochemistry, RNA structural biology, and spectroscopic techniques; 2) contributions to the PI's strength as a classroom teacher (for which she won an undergraduate Teaching Award in 2004), and expansion of a research-based course in Nucleic Acid Structure & Function developed by the PI; 3) recruiting visits to small liberal arts undergraduate colleges, targeting women's and historically black schools; 4) encouragement of women and minority students to pursue careers in science. This latter area takes the form of bringing minority undergraduates into the laboratory and department for summer research internships, sponsoring minority students and postdoctoral fellows for fellowships to do research in her laboratory. The PI has recently moved her laboratory from Florida State University to Hunter College of the City University of New York (CUNY), where her group will have access to outstanding research facilities, specifically a new nuclear magnetic resonance (NMR) spectrometer in a completely renovated NMR facility. Hunter is a minority serving institution with 65% women students that graduates 5% of the nation's Ph.D.s in the physical sciences.
This proposal is being co-funded by the Genes & Genomes Systems Cluster and the Biomolecular Systems Cluster.
