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