Hinge stiffness is a barrier to RNA folding

J Mol Biol. 2008 Jun 13;379(4):859-70. doi: 10.1016/j.jmb.2008.04.013. Epub 2008 Apr 10.

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 formati

MeSH terms

  • Animals
  • Base Sequence
  • Hydroxyl Radical / chemistry
  • Kinetics
  • Magnesium / pharmacology
  • Models, Molecular
  • Molecular Sequence Data
  • Nucleic Acid Conformation* / drug effects
  • Osmolar Concentration
  • RNA / chemistry*
  • RNA, Catalytic / chemistry
  • RNA, Catalytic / genetics
  • RNA, Protozoan / chemistry
  • RNA, Protozoan / genetics
  • Scattering, Small Angle
  • Tetrahymena thermophila / chemistry
  • Tetrahymena thermophila / enzymology
  • Tetrahymena thermophila / genetics
  • X-Ray Diffraction

Substances

  • RNA, Catalytic
  • RNA, Protozoan
  • Hydroxyl Radical
  • RNA
  • Magnesium