title: Slowdown of Interhelical Motions Induces a Glass Transition in RNA.
abstract: RNA function depends crucially on the details of its dynamics. The simplest RNA dynamical unit is a two-way interhelical junction. Here, for such a unit--the transactivation response RNA element--we present evidence from molecular dynamics simulations, supported by nuclear magnetic resonance relaxation experiments, for a dynamical transition near 230 K. This glass transition arises from the freezing out of collective interhelical motional modes. The motions, resolved with site-specificity, are dynamically heterogeneous and exhibit non-Arrhenius relaxation. The microscopic origin of the glass transition is a low-dimensional, slow manifold consisting largely of the Euler angles describing interhelical reorientation. Principal component analysis over a range of temperatures covering the glass transition shows that the abrupt slowdown of motion finds its explanation in a localization transition that traps probability density into several disconnected conformational pools over the low-dimensional energy landscape. Upon temperature increase, the probability density pools then flood a larger basin, akin to a lakes-to-sea transition. Simulations on transactivation response RNA are also used to backcalculate inelastic neutron scattering data that match previous inelastic neutron scattering measurements on larger and more complex RNA structures and which, upon normalization, give temperature-dependent fluctuation profiles that overlap onto a glass transition curve that is quasi-universal over a range of systems and techniques.
authors.affiliation: Department of Chemistry, University of California at Irvine, Irvine, California.
authors.forename: Aaron T
authors.initials: AT
authors.lastname: Frank
authors.affiliation: The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, Duke University School of Medicine, Durham, North Carolina.
authors.forename: Hashim M
authors.initials: HM
authors.lastname: Al-Hashimi
authors.affiliation: Department of Chemistry, University of California at Irvine, Irvine, California. Electronic address: andricio@uci.edu.
authors.forename: Ioan
authors.initials: I
authors.lastname: Andricioaei
mesh_terms: D001483:Base Sequence; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D012313:RNA / Q000737:chemistry*; D020218:Response Elements; D058989:Vitrification
chemical_list: D012313:RNA