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RNA Structure, Function and Dynamics; NMR Spectroscopy of RNA and Macromolecular Complexes; Biochemistry of RNA catalysis

Research in the Butcher Laboratory is focused on understanding how RNA molecules regulate gene expression. We aim to understand the three-dimensional structure, function and dynamics of RNA. RNA plays a central role in many biologically important processes, including protein synthesis, pre-messenger RNA (pre-mRNA) splicing, chromosome maintenance and viral replication. RNA molecules directly regulate gene expression inside the cell in a number of fascinating ways.

One of the on-going projects in our laboratory involves determining the structures of spliceosomal RNA complexes involved in pre-mRNA splicing, a critical step in eukaryotic gene expression. Another project involves understanding how a specific region of the HIV-1 viral genome RNA, termed the frameshift site, regulates the downstream expression of viral genes. A third project is to determine the thermodynamic driving forces responsible for the assembly of large RNAs into complex three-dimensional shapes. Investigating the structure and function of these RNAs yields important insights into how RNA functions in vivo, and why certain sequences or motifs have been selected by evolution.

We apply both biophysical and biochemical techniques, with a strong emphasis in NMR spectroscopy. NMR is ideally suited for both atomic resolution structure determination and the study of dynamic processes in solution. Multidimensional, heteronuclear NMR spectroscopy combined with selective isotopic labeling is a powerful method for investigating the structure of RNA and its interactions with other molecules.