Kinetic intermediates trapped by native interactions in RNA folding

D K Treiber; M S Rook; P P Zarrinkar; J R Williamson

doi:10.1126/science.279.5358.1943

Kinetic intermediates trapped by native interactions in RNA folding

Science. 1998 Mar 20;279(5358):1943-6. doi: 10.1126/science.279.5358.1943.

Authors

D K Treiber¹, M S Rook, P P Zarrinkar, J R Williamson

Affiliation

¹ Department of Molecular Biology, MB33, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

PMID: 9506945
DOI: 10.1126/science.279.5358.1943

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Binding Sites
Kinetics
Magnesium / metabolism
Models, Molecular
Mutation
Nucleic Acid Conformation*
RNA, Catalytic / chemistry*
RNA, Catalytic / genetics
RNA, Catalytic / metabolism
Tetrahymena / chemistry

Substances

RNA, Catalytic
Magnesium