The Role of Helix Topology and Counterion Distributions in RNA Interactions

Abstract

RNA and DNA helices have the same charge, −2e/bp, but different helical structures. The 2′-OH present in RNA hinders duplex flexibility and promotes the A-form helix whereas the more malleable and polymorphic DNA duplexes prefer the B-form. Using a combination of experimental and computational approaches, we show that the topology of the A-form helix alters the spatial distribution of counterions and is essential in promoting the charge screening efficiency of RNA helices. Results from Anomalous Small-Angle X-ray Scattering (ASAXS) experiments suggest that monovalent and divalent cations are more closely localized to the RNA central axis due to A-form major groove penetration. This leads to very efficient change screening in RNA helices which has implications for ion-mediated RNA interactions in two important areas: RNA folding reactions and the design of short RNA helices for RNA interference applications.