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

TL;DR

This paper discusses how single molecule pulling experiments combined with theory and simulations can elucidate the folding landscapes and dynamics of non-coding RNAs, highlighting applications to riboswitches and their assembly principles.

Contribution

It introduces a quantitative approach integrating experiments, theory, and simulations to study RNA folding landscapes and reveals the limitations of current experimental techniques.

Findings

RNA folding landscapes can be probed using single molecule pulling experiments.

RNA assembly is governed by the stability of individual helices.

Limitations exist in extracting detailed folding parameters from molecular extension data.

Abstract

Non-coding 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 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 non-coding RNA elements that control gene expression by undergoing dynamical conformational changes in response to binding of metabolites, lead to an organization principle that 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.