Real-time control of the energy landscape by force directs the folding of RNA molecules.
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.
Li
Pan T X
PT
Department of Chemistry, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA. panli@albany.edu
Bustamante
Carlos
C
Tinoco
Ignacio
I
D001483:Base Sequence; D001696:Biomechanical Phenomena; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D052898:Optical Tweezers; D012313:RNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D038621:Regulatory Sequences, Ribonucleic Acid; D013816:Thermodynamics; D013997:Time Factors
D038621:Regulatory Sequences, Ribonucleic Acid; D012313:RNA