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Visualizing the formation of an RNA folding intermediate through a fast highly modular secondary structure switch

Author

Listed:
  • Yi Xue

    (Duke Center for RNA Biology, Duke University Medical Center)

  • Brant Gracia

    (Institute for Cellular and Molecular Biology, University of Texas at Austin)

  • Daniel Herschlag

    (Beckman Center, Stanford University
    Stanford University
    Stanford University
    Chemistry, Engineering, and Medicine for Human Health (ChEM-H) Institute, Stanford University)

  • Rick Russell

    (Institute for Cellular and Molecular Biology, University of Texas at Austin)

  • Hashim M. Al-Hashimi

    (Duke Center for RNA Biology, Duke University Medical Center
    Duke University, Durham)

Abstract

Intermediates play important roles in RNA folding but can be difficult to characterize when short-lived or not significantly populated. By combining 15N relaxation dispersion NMR with chemical probing, we visualized a fast (kex=k1+k−1≈423 s−1) secondary structural switch directed towards a low-populated (∼3%) partially folded intermediate in tertiary folding of the P5abc subdomain of the ‘Tetrahymena’ group I intron ribozyme. The secondary structure switch changes the base-pairing register across the P5c hairpin, creating a native-like structure, and occurs at rates of more than two orders of magnitude faster than tertiary folding. The switch occurs robustly in the absence of tertiary interactions, Mg2+ or even when the hairpin is excised from the three-way junction. Fast, highly modular secondary structural switches may be quite common during RNA tertiary folding where they may help smoothen the folding landscape by allowing folding to proceed efficiently via additional pathways.

Suggested Citation

  • Yi Xue & Brant Gracia & Daniel Herschlag & Rick Russell & Hashim M. Al-Hashimi, 2016. "Visualizing the formation of an RNA folding intermediate through a fast highly modular secondary structure switch," Nature Communications, Nature, vol. 7(1), pages 1-11, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11768
    DOI: 10.1038/ncomms11768
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    Cited by:

    1. Ge Han & Yi Xue, 2022. "Rational design of hairpin RNA excited states reveals multi-step transitions," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Ainan Geng & Laura Ganser & Rohit Roy & Honglue Shi & Supriya Pratihar & David A. Case & Hashim M. Al-Hashimi, 2023. "An RNA excited conformational state at atomic resolution," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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