Hinge Stiffness Is a Barrier to RNA Folding

Jörg C. Schlatterer, Lisa W. Kwok, Jessica S. Lamb, Hye Yoon Park, Kurt Andresen, Michael Brenowitz, Lois Pollack

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Cation-mediated RNA folding from extended to compact, biologically active conformations relies on a temporal balance of forces. The Mg2 +-mediated folding of the Tetrahymena thermophila ribozyme is characterized by rapid nonspecific collapse followed by tertiary-contact-induced compaction. This article focuses on an autonomously folding portion of the Tetrahymena ribozyme, its P4-P6 domain, in order to probe one facet of the rapid collapse: chain flexibility. The time evolution of P4-P6 folding was followed by global and local measures as a function of Mg2 + concentration. While all concentrations of Mg2 + studied are sufficient to screen the charge on the helices, the rates of compaction and tertiary contact formation diverge as the concentration of Mg2 + increases; collapse is greatly accelerated by Mg2 +, while tertiary contact formation is not. These studies highlight the importance of chain stiffness to RNA folding; at 10 mM Mg2 +, a stiff hinge limits the rate of P4-P6 folding. At higher magnesium concentrations, the rate-limiting step shifts from hinge bending to tertiary contact formation.

Original languageEnglish (US)
Pages (from-to)859-870
Number of pages12
JournalJournal of Molecular Biology
Volume379
Issue number4
DOIs
StatePublished - Jun 13 2008

Keywords

  • RNA folding
  • compaction
  • persistence length
  • time-resolved hydroxyl radical footprinting
  • time-resolved small-angle X-ray scattering

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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    Schlatterer, J. C., Kwok, L. W., Lamb, J. S., Park, H. Y., Andresen, K., Brenowitz, M., & Pollack, L. (2008). Hinge Stiffness Is a Barrier to RNA Folding. Journal of Molecular Biology, 379(4), 859-870. https://doi.org/10.1016/j.jmb.2008.04.013