Memory Effects in RNA Folding Dynamics Revealed by Single-Molecule Fluorescence

Abstract

RNA molecules are biopolymers that play numerous essential roles in all basic cellular processes. To perform their functions, they must fold into the correct three-dimensional structures. RNA folding potential energy surfaces are rugged and full of kinetic traps, which can prevent the formation of the native structure and result in persistent differences in behavior between molecules, termed folding memory effects. In this review, we revisit the discovery of persistent memory effects in folding of RNA molecules. The study of memory effects is closely linked to the development and application of single-molecule fluorescence methods, which were instrumental in the dissection of RNAs into discrete subpopulations with different dynamic properties. We explore possible hypotheses that account for memory effects such as secondary structure differences, surface immobilization effects, and metal ions. The ability to interconvert subpopulations confirms that memory effects are an intrinsic property of RNA folding and enables their thermodynamic and kinetic characterization.