Perturbed folding kinetics of circularly permuted RNAs with altered topology

Susan L. Heilman-Miller, Sarah A. Woodson

Research output: Contribution to journalArticlepeer-review

Abstract

The folding pathway of the Tetrahymena ribozyme correlates inversely with the sequence distance between native interactions, or contact order. The rapidly folding P4-P6 domain has a low contact order, while the slowly folding P3-P7 region has a high contact order. To examine the role of topology and contact order in RNA folding, we screened for circular permutants of the ribozyme that retain catalytic activity. Permutants beginning in the P4-P6 domain fold 5 to 20 times more slowly than the wild-type ribozyme. By contrast, 50% of a permuted RNA that disjoins a non-native interaction in P3 folds tenfold faster than the wild-type ribozyme. Hence, the probability of rapidly folding to the native state depends on the topology of tertiary domains.

Original languageEnglish (US)
Pages (from-to)385-394
Number of pages10
JournalJournal of molecular biology
Volume328
Issue number2
DOIs
StatePublished - Apr 25 2003

Keywords

  • BSA, bovine serum albumen
  • Circular permutation
  • Group I intron
  • RNA folding
  • Ribozyme

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Molecular Biology

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