RNA under Tension: Folding Landscapes, Kinetic Partitioning Mechanism, and Molecular Tensegrity

Noncoding RNA sequences play a great role in controlling a number of cellular functions, thus raising the need to understand their complex conformational dynamics in quantitative detail. In this Perspective, we first show that single-molecule pulling experiments when combined with theory and simulations can be used to quantitatively explore the folding landscape of nucleic acid hairpins, and riboswitches with tertiary interactions. Applications to riboswitches, which are noncoding RNA elements that control gene expression by undergoing dynamical conformational changes in response to binding of metabolites, lead to an organization principle in which assembly of RNA is determined by the stability of isolated helices. We also point out the limitations of single-molecule pulling experiments, with molecular extension as the only accessible parameter, in extracting key parameters of the folding landscapes of RNA molecules.