Entropic stabilization of the folded states of RNA due to macromolecular crowding

TL;DR

This paper reviews how macromolecular crowding influences RNA folding, particularly the equilibrium between different conformations, highlighting the importance of crowder size and ionic conditions in stabilizing folded states.

Contribution

It provides a comprehensive analysis of crowding effects on RNA folding, emphasizing the role of excluded volume interactions and their impact on RNA conformational stability.

Findings

Crowding significantly affects RNA folding when crowder size is smaller than RNA's radius of gyration.

Macromolecular crowding alters the equilibrium between pseudoknot and hairpin states.

Crowding effects are modulated by ionic strength and influence enzyme activity.

Abstract

We review the effects of macromolecular crowding on the folding of RNA by considering the simplest scenario when excluded volume interactions between crowding particles and RNA dominate. Using human telomerase enzyme as an example, we discuss how crowding can alter the equilibrium between pseudoknot and hairpin states of the same RNA molecule - a key aspect of crowder-RNA interactions. We summarize data showing that the crowding effect is significant only if the size of the spherical crowding particle is smaller than the radius of gyration of the RNA in the absence of crowding particles. The implication for function of the wild type and mutants of human telomerase is outlined by using a relationship between enzyme activity and its conformational equilibrium. In addition, we discuss the interplay between macromolecular crowding and ionic strength of the RNA buffer. Finally, we briefly review recent experiments which illustrate the connection between excluded volume due to macromolecular crowding and the thermodynamics of RNA folding.