TY - JOUR T1 - Salt Effects on the Thermodynamics of a Frameshifting RNA Pseudoknot under Tension JF - bioRxiv DO - 10.1101/048801 SP - 048801 AU - Naoto Hori AU - Natalia A. Denesyuk AU - D. Thirumalai Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/04/15/048801.abstract N2 - One of the key factors in -1 programmed ribosomal frameshifting (PRF) is a pseu-doknot (PK) RNA. A number of single molecule experiments have been performed on PKs to decipher the mechanism of PRF. Motivated by the experiments, we performed simulations to describe the response of a PK over a range of mechanical forces (ƒs) and monovalent salt concentrations (Cs). The coarse-grained simulations quantitatively reproduces the multistep thermal melting. The free energy changes obtained in simulations are in excellent agreement with experiments, thus validating our model. The predicted phase diagram shows that a sequence of structural transitions, populating distinct intermediates, occur as ƒ and C are changed. The stem-loop tertiary interactions rupture first followed by unfolding of the 3′-end hairpin (U⇌I). Finally, the 5′-end hairpin unravels producing a stretched state (I⇌F). A theoretical analysis of the phase boundaries shows that the critical force for rupture scales as (log Cm)α with α = 1 (0.5) for U⇌I (I⇌F) transition. This relation is used to obtain the ion-preferential coefficients, which shows that ion-RNA interactions can be quantitatively measured in single molecule experiments. Our simulations predict a plausible link between the stability of the 5′ hairpin and efficiency of PRF. ER -