Abstract
Most large RNAs achieve their active, native structures only as complexes with one or more cofactor proteins. By varying the Mg2+ concentration, the catalytic core of the bI5 group I intron RNA can be manipulated into one of three states, expanded, collapsed or native, or into balanced equilibria between these states. Under near-physiological conditions, the bI5 RNA folds rapidly to a collapsed but non-native state. Hydroxyl radical footprinting demonstrates that assembly with the CBP2 protein cofactor chases the RNA from the collapsed state to the native state. In contrast, CBP2 also binds to the RNA in the expanded state to form many non-native interactions. This structural picture is reinforced by functional splicing experiments showing that RNA in an expanded state forms a non-productive, kinetically trapped complex with CBP2. Thus, rapid folding to the collapsed state functions to self-chaperone bI5 RNA folding by preventing premature interaction with its protein cofactor. This productive, self-chaperoning role for RNA collapsed states may be especially important to avert misassembly of large multi-component RNA–protein machines in the cell.
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Acknowledgements
This work was supported by grants from the Searle Scholars Program of the Chicago Community Trust and by the NIH to K.M.W. We thank E. Westhof and C. Massire for modeling the bI5 group I intron RNA and P. Bevilacqua, M. Redinbo and K. Buchmueller for comments on the manuscript.
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Webb, A., Weeks, K. A collapsed state functions to self-chaperone RNA folding into a native ribonucleoprotein complex. Nat Struct Mol Biol 8, 135–140 (2001). https://doi.org/10.1038/84124
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DOI: https://doi.org/10.1038/84124
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