Maximizing RNA folding rates: A balancing act

D. Thirumalai, Sarah A. Woodson

Research output: Contribution to journalReview article

Abstract

Large ribozymes typically require very long times to refold into their active conformation in vitro, because the RNA is easily trapped in metastable misfolded structures. Theoretical models show that the probability of misfolding is reduced when local and long-range interactions in the RNA are balanced. Using the folding kinetics of the Tetrahymena ribozyme as an example, we propose that folding rates are maximized when the free energies of forming independent domains are similar to each other. A prediction is that the folding pathway of the ribozyme can be reversed by inverting the relative stability of the tertiary domains. This result suggests strategies for optimizing ribozyme sequences for therapeutics and structural studies.

Original languageEnglish (US)
Pages (from-to)790-794
Number of pages5
JournalRNA
Volume6
Issue number6
DOIs
StatePublished - Jun 1 2000

Keywords

  • Group I intron
  • RNA folding
  • RNA structure
  • Ribozyme

ASJC Scopus subject areas

  • Molecular Biology

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    Thirumalai, D., & Woodson, S. A. (2000). Maximizing RNA folding rates: A balancing act. RNA, 6(6), 790-794. https://doi.org/10.1017/S1355838200000522