Book of Abstracts: Albany 2007

category image Albany 2007
Conversation 15
June 19-23 2007

Real-Time Control of the Energy Landscape by Force Directs the Folding of Single RNA Molecules

The folding energy landscapes of RNAs are more rugged than those of proteins, displaying many local minima and lacking the single global minimum that dominates the folding potential of polypeptides. As a result, RNAs can fold into several alternative secondary structures of similar stabilities, and it remains unclear how RNAs discriminate among this ensemble of competing conformations in their search for the native state. Using optical tweezers, we show here that the folding energy landscape can be manipulated to control the fate of an RNA: individual RNA molecules can be induced into either native or misfolding pathways by modulating the relaxation rate of applied force. Furthermore, by adjusting force at the appropriate time during the folding process, it is possible to redirect the folding trajectory of a molecule and encourage its structural re-arrangements from kinetically-trapped intermediates to the native structure. Thus, single molecule manipulation methods provide a novel way to directly influence the RNA folding pathways, and to survey the manifold of folding trajectories and intermediates of RNAs in great detail, a capability previously reserved only for theoretical studies.

Pan TX Li1,4,*
Carlos Bustamante1,2,3
Ignacio Tinoco, Jr.1

1Department of Chemistry
2Departments of Physics and Molecular and Cell Biology
3Howard Hughes Medical Institute
University of California
Berkeley, CA 94720, USA
4Present address:
Department of Biological Sciences
University at Albany
State University of New York
Albany, NY

*Phone: (518) 591-8879
Email: panli@albany.edu