A THERMODYNAMIC DESCRIPTION OF CATION-RNA INTERACTIONS WITH DIFFERING ION ATMOSPHERE COMPOSITION
Embargo until
2015-08-01
Date
2014-07-23
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Johns Hopkins University
Abstract
The charged nature of nucleic acids imposes a strong relationship between cations and RNA structure. As a result, RNA folding efficiency is highly dependent on the quantity and types of cations in solution. In vivo, there are a multitude of cations available to interact with RNA. The principal monovalent cation, K+, serves to neutralize most of the negative charges derived from nucleic acids. In addition, there are cations of higher valence that perform a number of important functions. Many studies have confirmed the ability of Mg2+ to promote native RNA structure. In addition to K+ and Mg2+, organic cations (polyamines) such as putrescine2+, spermidine3+, and spermine4+ are believed to be important for the process of RNA folding. All of these cations, both organic and inorganic, differ dramatically in both structural and physical properties. The purpose of the current work is to i) determine if organic and inorganic divalent cations stabilize the same folded state, ii) determine how different divalent ions interact with RNA to promote folding, and iii) develop an understanding of how the ion atmosphere is organized in the presence of three distinct types of cations (K+, Mg2+ and putrescine2+).
To pursue these goals, a set of RNAs, all characterized at atomic resolution, were selected to represent a range of selectivity for inorganic ions. This structural information, combined with thermodynamic analyses looking at Mg2+ excess, thermal stability, ligand binding, and folding efficiency provide a comprehensive look at how ions stabilize the native state of RNA. We find that RNAs with Mg2+ chelation sites require either Mg2+ or Ca2+ to properly fold, while putrescine2+ can stabilize the native state of non-chelators, albeit to a lesser degree than Mg2+. Measurement of Mg2+ excess with the native and intermediate states shows that Mg2+ is more effective at stabilizing native structure due to a closer approach to the RNA surface. Therefore, organization of the ion atmosphere is dependent on the types of ions in solution as well as the conformation of the RNA.
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RNA folding