Many non-coding RNAs must fold into specific three-dimensional structures.  In the cell, the stability of the folded RNA depends on its interactions with ions and with other solutes that take up 30% of the available volume. Using small angle X-ray scattering to measure the folding of a bacterial group I ribozyme, we find that molecular crowding equivalent to what is present in real cells stabilizes RNA tertiary structures by several kcal/mol. Systematic perturbations to scattering functions and experiments at different temperatures show this stabilization is partly due to reduced conformational entropy of the unfolded RNA.  Compression of the native state ensemble in crowded solutions correlates with an increase in ribozyme catalytic activity.  Consequently, the ribozyme reaches its catalytically active structure at much lower Mg2+ concentrations in a crowded milieu than in a dilute solution.

RNA folding in crowded solutions

245th National Meeting (2013)

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