|
 |
 |
 |
 |
 |
 |
 |
 |
|
|
 |
|
Biological
Complexity
Genomics and proteomics approaches are revolutionizing biology by systematically identifying all the genes and gene products within an organism and by suggesting functions for many of the gene products. Nevertheless, large challenges will remain in the post-genomic era: we will still need to understand how the gene products, both proteins and RNA, perform their functions. Such understanding will be challenged by the complexity of the biological processes and because many of these processes are mediated by large, multi-component 'enzyme machines' that must assemble from individual subunits into a functional form.
|
|
An experimental approach with enormous power has recently been developed: single molecules or machines can be observed instead of the vast ensembles studied in conventional approaches. Studying single molecules is remarkably powerful for dissecting complex processes because it is possible to detect intermediate structures and reaction steps that are typically hidden in the population averaging that is intrinsic to conventional experiments. |
|
|
RNA-Protein Enzymes
Of all the enzyme machines found in nature, some of the most complex and important are composed of both RNA and protein subunits. These include the spliceosome, which processes messenger RNAs, and the ribosome, which produces proteins from the spliced mRNAs. The presence of RNA in these machines introduces a challenge: the RNA components must fold and assemble with the protein components. This is a challenge because RNA is expected to have basic limitations in its abilities to specify a single native structure and to fold rapidly to that native structure.
|
RNA Folding Landscape
|
The goal of our research is to obtain a quantitative and rigorous molecular understanding of the processes and principles that govern RNA folding and assembly with proteins. Our current focus is on comparatively simple RNA-protein enzymes such as group I introns and their protein co-factors. These RNA-protein complexes have the advantage that they are readily manipulated and therefore experimentally tractable, but at the same time they are sufficiently large and complex that their behavior is likely to yield principles that are also applicable to more complex machines.
|
|
RNA Chaperone Proteins
In addition to proteins that assemble as part of functional RNA-protein complexes, RNAs are likely to have a general requirement for chaperone proteins. The proteins interact with RNA as they folds, and function to prevent or resolve misfolded intermediates. A particularly interesting class of chaperone proteins is the DExD/H box proteins, which couple ATP binding and hydrolysis to RNA conformational rearrangements. We are currently investigating how DExD/H box proteins function as RNA chaperones and how they are directed to their physiological RNA and RNP substrates. For all our research we are combining the single molecule approach with conventional biochemical and biophysical methods to obtain the fullest understanding possible.
|
|
|
 |
 |
 |
|
 |
| |
|
 |
 |
|
|
