Taming free energy landscapes with RNA chaperones

Many non-coding RNAs fold into complex three-dimensional structures, yet the self-assembly of RNA structure is hampered by mispairing, weak tertiary interactions, electrostatic barriers, and the frequent requirement that the 5′ and 3′ ends of the transcript interact. This rugged free energy landscape for RNA folding means that some RNA molecules in a population rapidly form their native structure, while many others become kinetically trapped in misfolded conformations. Transient binding of RNA chaperone proteins destabilize misfolded intermediates and lower the transition states between conformations, producing a smoother landscape that increases the rate of folding and the probability that a molecule will find the native structure. DEAD-box proteins couple the chemical potential of ATP hydrolysis with repetitive cycles of RNA binding and release, expanding the range of conditions under which they can refold RNA structures.