Hierarchy and dynamics of RNA folding

The evidence showing that the self-assembly of complex RNAs occurs in discrete transitions, each relating to the folding of sub-systems of increasing size and complexity starting from a state with most of the secondary structure, is reviewed. The reciprocal influence of the concentration of magnesium ions and nucleotide mutations on tertiary structure is analyzed. Several observations demonstrate that detrimental mutations can be rescued by high magnesium concentrations, while stabilizing mutations lead to a lesser dependence on magnesium ion concentration. Recent data point to the central controlling and monitoring roles of RNA-binding proteins that can bind to the different folding stages, either before full establishment of the secondary structure or at the molten globule state before the cooperative transition to the final three-dimensional structure.