Measurement of the Deuterium Kinetic Isotope Effect on Hydroxyl Radical Cleavage of RNA

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This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).The recent completion of the sequences of the human genome, and many others, has provided the raw data on which to build a deep understanding of how living organisms work. But more than just the sequence of DNA nucleotides in the genome is needed to understand how genetic information is retrieved and expressed. A key player in the transmission of genetic information is ribonucleic acid, RNA. The shape of an RNA molecule is critical to its function in the life of the cell, yet few methods are capable of mapping the structure of RNA. This project will develop a new experimental method for determining RNA structure that makes use of the hydroxyl radical, a high-resolution chemical probe of the structure of nucleic acid molecules. The new method is designed to provide atom-specific information on the structural features of RNA. The result will be a chemical probe of RNA structure of unprecedented resolution.Broader impacts. Since RNA molecules are ubiquitous in all living organisms, the new structural method that will result from this research will find wide application in laboratories around the world that seek to understand the role of RNA in biology. The graduate students who will work on this project will be trained to take a highly quantitative approach to experiments that normally are interpreted qualitatively. They will learn to combine synthetic and physical chemistry with structural and molecular biology. This research project was originally developed by two Postdoctoral Faculty Fellows (PFFs), each of whom has since been appointed as Assistant Professor of Chemistry at an undergraduate institution. The PFF program is an innovative program in the Chemistry Department at Boston University that is focused on preparing recent Ph.D.s to teach chemistry and to mentor research at undergraduate colleges. Half the time of a PFF is spent on research and half on teaching. New PFFs will be sought to join this project. The Tullius laboratory has focused in recent years on outreach to high school students and undergraduates to provide them with research experience in an active university laboratory. In summer 2009, four high school students and an undergraduate will do research in the Tullius lab alongside postdoctoral fellows and graduate students.