Principles of RNA compaction: Insights from the equilibrium folding pathway of the P4-P6 RNA domain in monovalent cations

Keiji Takamoto, Rhiju Das, Qin He, Sebastian Doniach, Michael Brenowitz, Daniel Herschlag, Mark R. Chance

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89 Scopus citations


Counterions are required for RNA folding, and divalent metal ions such as Mg2+ are often critical. To dissect the role of counterions, we have compared global and local folding of wild-type and mutant variants of P4-P6 RNA derived from the Tetrahymena group I ribozyme in monovalent and in divalent metal ions. A remarkably simple picture of the folding thermodynamics emerges. The equilibrium folding pathway in monovalent ions displays two phases. In the first phase, RNA molecules that are initially in an extended conformation enforced by charge-charge repulsion are relaxed by electrostatic screening to a state with increased flexibility but without formation of long-range tertiary contacts. At higher concentrations of monovalent ions, a state that is nearly identical to the native folded state in the presence of Mg2+ is formed, with tertiary contacts that involve base and backbone interactions but without the subset of interactions that involve specific divalent metal ion-binding sites. The folding model derived from these and previous results provides a robust framework for understanding the equilibrium and kinetic folding of RNA.

Original languageEnglish (US)
Pages (from-to)1195-1206
Number of pages12
JournalJournal of Molecular Biology
Issue number5
StatePublished - Nov 5 2004



  • P4-P6 domain
  • RNA folding
  • compaction
  • electrostatic relaxation
  • tertiary interaction formation

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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