Urea destabilizes RNA by forming stacking interactions and multiple hydrogen bonds with nucleic acid bases

TL;DR

This study uses molecular dynamics simulations to reveal how urea destabilizes RNA by forming hydrogen bonds and stacking interactions with bases, providing detailed atomic insights into the denaturation process.

Contribution

It uncovers the atomic-level mechanisms of urea-induced RNA destabilization, including stacking interactions and hydrogen bonding, and estimates the m-value for RNA.

Findings

Urea forms multiple hydrogen bonds with RNA bases.

Urea engages in stacking interactions with bases.

The study estimates the m-value for RNA-urea interactions.

Abstract

Urea titration of RNA by urea is an effective approach to investigate the forces stabilizing this biologically important molecule. We used all atom molecular dynamics simulations using two urea force fields and two RNA constructs to elucidate in atomic detail the destabilization mechanism of folded RNA in aqueous urea solutions. Urea denatures RNA by forming multiple hydrogen bonds with the RNA bases and has little influence on the phosphodiester backbone. Most significantly we discovered that urea engages in stacking interactions with the bases. We also estimate, for the first time, m-value for RNA, which is a measure of the strength of urea-RNA interactions. Our work provides a conceptual understanding of the mechanism by which urea enhances RNA folding rates.