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Science 20 March 1998:
Vol. 279. no. 5358, pp. 1943 - 1946
DOI: 10.1126/science.279.5358.1943
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Reports

Kinetic Intermediates Trapped by Native Interactions in RNA Folding

Daniel K. Treiber, Martha S. Rook, Patrick P. Zarrinkar, * James R. Williamson dagger

In the magnesium ion-dependent folding of the Tetrahymena ribozyme, a kinetic intermediate accumulates in which the P4-P6 domain is formed, but the P3-P7 domain is not. The kinetic barriers to P3-P7 formation were investigated with the use of in vitro selection to identify mutant RNA molecules in which the folding rate of the P3-P7 domain was increased. The critical mutations disrupt native tertiary interactions within the P4-P6 domain and increase the rate of P3-P7 formation by destabilizing a kinetically trapped intermediate. Hence, kinetic traps stabilized by native interactions, and not simply by mispaired nonnative structures, can present a substantial barrier to RNA folding.

D. K. Treiber and J. R. Williamson, Department of Molecular Biology, MB33, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
M. S. Rook and P. P. Zarrinkar, Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
*   Present address: Center for Cellular and Genetic Therapies, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.

dagger    To whom correspondence should be addressed.

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