Decrease in RNA Folding Cooperativity by Deliberate Population of Intermediates in RNA G-Quadruplexes

摘要

RNA folding is central to diverse biological and chemical processes, including gene regulation and biosensing. Cooperativity is a key feature of RNA folding, and critical to the folding of small and large RNAs alike and to the response of naturally occurring riboswitches. Some biological RNAs fold with little or no cooperativity, whereas others exhibit high cooperativity (i.e., steep folding transitions). Concerning biosensing, conventional or "classical" biosensors without cooperative behavior bind an analyte with a responsive range of approximately 100-fold in analyte concentration, using 10-90 % of the maximal signal. When the analyte concentration is above or below this range, however, "dead zones" are found wherein the sensor will not work; as such, biosensors with extended dynamic ranges are needed. Integrating negative (or "anti-") cooperativity into RNA folding provides one way of achieving this outcome. The goals of our study were to gain new fundamental insights into the folding of biological RNAs and to aid the development of biosensors with diverse response ranges through the development of a series of RNA scaffolds with tunable cooperativity.