Salt Effects on the Thermodynamics of a Frameshifting RNA Pseudoknot under Tension.

ABSTRACT: Because of the potential link between -1 programmed ribosomal frameshifting and response of a pseudoknot (PK) RNA to force, a number of single-molecule pulling experiments have been performed on PKs to decipher the mechanism of programmed ribosomal frameshifting. Motivated in part by these experiments, we performed simulations using a coarse-grained model of RNA to describe the response of a PK over a range of mechanical forces (fs) and monovalent salt concentrations (Cs). The coarse-grained simulations quantitatively reproduce the multistep thermal melting observed in experiments, thus validating our model. The free energy changes obtained in simulations are in excellent agreement with experiments. By varying f and C, we calculated the phase diagram that shows a sequence of structural transitions, populating distinct intermediate states. As f and C are changed, the stem-loop tertiary interactions rupture first, followed by unfolding of the 3'-end hairpin (I?F). Finally, the 5'-end hairpin unravels, producing an extended state (E?I). A theoretical analysis of the phase boundaries shows that the critical force for rupture scales as (logCm)(?) with ?=1(0.5) for E?I (I?F) transition. This relation is used to obtain the preferential ion-RNA interaction coefficient, which can be quantitatively measured in single-molecule experiments, as done previously for DNA hairpins. A by-product of our work is the suggestion that the frameshift efficiency is likely determined by the stability of the 5'-end hairpin that the ribosome first encounters during translation.

SUBMITTER: Hori N 

PROVIDER: S-EPMC5590673 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature