Real-time control of the energy landscape by force directs the folding of RNA molecules

Departments of *Chemistry and
^¶Physics and Molecular and Cell Biology,
^‖Howard Hughes Medical Institute, University of California, Berkeley, CA 94720

Contributed by Ignacio Tinoco, Jr., March 9, 2007 (received for review January 30, 2007)

Abstract

The rugged folding-energy landscapes of RNAs often display many competing minima. How do RNAs discriminate among competing conformations in their search for the native state? By using optical tweezers, we show 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 and even be redirected during the folding process to switch from misfolding to native folding pathways. Controlling folding pathways at the single-molecule level provides a way to survey the manifold of folding trajectories and intermediates, a capability that previously was available only to theoretical studies.

Footnotes

^§To whom correspondence may be addressed. E-mail: intinoco{at}lbl.gov or panli{at}albany.edu
Author contributions: P.T.X.L., C.B., and I.T. designed research; P.T.X.L. performed research; P.T.X.L. and I.T. analyzed data; and P.T.X.L., C.B., and I.T. wrote the paper.
↵ ^†Present address: Department of Biological Sciences, University at Albany, State University of New York, Albany, NY 12222.
The authors declare no conflict of interest.
Abbreviation:

TAR,

transactivation response region.