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

Yi Xue, Brant Gracia, Daniel Herschlag, Rick Russell and Hashim M. Al-Hashimi ()
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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
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

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms11768

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