Single-molecule mechanical unfolding and folding of a pseudoknot in human telomerase RNA

RNA. 2007 Dec;13(12):2175-88. doi: 10.1261/rna.676707. Epub 2007 Oct 24.

Abstract

RNA unfolding and folding reactions in physiological conditions can be facilitated by mechanical force one molecule at a time. By using force-measuring optical tweezers, we studied the mechanical unfolding and folding of a hairpin-type pseudoknot in human telomerase RNA in a near-physiological solution, and at room temperature. Discrete two-state folding transitions of the pseudoknot are seen at approximately 10 and approximately 5 piconewtons (pN), with ensemble rate constants of approximately 0.1 sec(-1), by stepwise force-drop experiments. Folding studies of the isolated 5'-hairpin construct suggested that the 5'-hairpin within the pseudoknot forms first, followed by formation of the 3'-stem. Stepwise formation of the pseudoknot structure at low forces are in contrast with the one-step unfolding at high forces of approximately 46 pN, at an average rate of approximately 0.05 sec(-1). In the constant-force folding trajectories at approximately 10 pN and approximately 5 pN, transient formation of nonnative structures were observed, which is direct experimental evidence that folding of both the hairpin and pseudoknot takes complex pathways. Possible nonnative structures and folding pathways are discussed.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cloning, Molecular
  • Freezing
  • Humans
  • Kinetics
  • Nucleic Acid Conformation
  • Operon
  • Protein Conformation
  • Protein Denaturation
  • Protein Folding
  • RNA / chemistry
  • RNA / genetics*
  • RNA / metabolism*
  • Telomerase / chemistry
  • Telomerase / genetics*
  • Telomerase / metabolism*

Substances

  • telomerase RNA
  • RNA
  • Telomerase