Dynamic conversion of RNA in crowded environments: implication of significance of micro-viscosity against molecular confinement

The conformational behavior of RNA in densely packed intracellular conditions is a long-standing area of interest and is critical for understanding biologically important dynamics in a living cell. The effect of viscosity at the solvent-accessible surface area on the concerted conformational motions of tRNA in crowded conditions must be considered. We have examined the effect of PEG-induced crowding on the internal dynamics of unfolded and folded tRNA using ps ~ ns Quasi-Elastic Neutron Scattering spectroscopy (QENS) to probe the role of the local micro-viscosity as a function of the molecular confinement effects from crowding. At temperatures lower than water crystallization (T_c) and higher than dynamic glass transition temperature (T_d) of tRNA, the conformational flexibility becomes larger with more confinement, and it is suppressed more strongly at higher temperatures. The dynamic conversion across T_c indicates the significance of the micro-viscosity versus molecular confinement, both of which can orthogonally vary with crowding conditions. Comparison of dynamics from QENS with the aid of molecular dynamics simulations provides insight into the physical origin of this dynamic conversion and its coupling with the local structure of water at the macromolecular surface.