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 journalArticlepeer-review

43 Scopus citations


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
Issue number4
StatePublished - Jun 13 2008
Externally publishedYes

Bibliographical note

Funding Information:
We thank Alec Sandy and Suresh Narayanan for their assistance at beamline 8-IDI at the Advanced Photon Source and Inna Shcherbakova and Somdeb Mitra for their assistance in initiating the time-resolved footprinting studies. This work was supported by grant P01-GM066275 from the National Institute of General Medical Sciences. Use of the Advanced Photon Source was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. W-31-109-Eng-38. We acknowledge additional support from the National Science Foundation through grant MCB-0347220 (to L.P.) and the Cornell Nanobiotechnology Center. Fabrication of the SAXS mixing devices was conducted in the Cornell Nanoscale Science and Technology Facility that is supported by the NSF, Cornell University and industrial affiliates.


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


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