The Butcher Lab

Structural dynamics within U6 RNA. The NMR structure of the U6 RNA intramolecular stem-loop at pH 7 (blue) and pH 6 (gold), superimposed over the catalytically essential internal loop region of U6 RNA (image courtesy of S. Butcher)

 
Research

The work in this laboratory focuses on understanding the structure, function and dynamics of RNA. RNA plays a central role in many biologically important processes, including peptide bond formation, pre-mRNA splicing, viral processing and maturation, and chromosome maintenance. It is becoming increasingly clear that in these and other systems, RNA performs the actual chemical or catalytic steps of the reactions.
 
One of the major areas of our research involves understanding the structure and mechanism of catalytic RNAs, or ribozymes. We would like to determine how an RNA folds into a three-dimensional active site, and to elucidate the thermodynamic properties that drive folding and catalysis. Additionally, it is important to understand how ions such as magnesium interact with RNA to facilitate folding and catalysis.
 
Other projects in the laboratory involve determining the structures of phylogenetically conserved RNA domains within complexes such as the spliceosome. Solving these types of RNA structures yields important insights into how RNA folds and why certain sequences or motifs persist during evolution Another project is to understand how mutations in mitochondrial tRNAs lead to genetic diseases.
 
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. Furthermore, it is the only method that can be used to directly observe hydrogen bond formation. Multidimensional, heteronuclear NMR spectroscopy combined with selective isotopic labeling is therefore a powerful method for solving and probing the structure of RNA and its complexes in solution.