Structure and dynamics of adenosine bulged RNA duplex reveals formation of the dinucleotide platform in the C:G-A triple

Abstract

The RNA single bulge motif is an unpaired residue within a strand of several complementary base pairs. Structure and dynamics of RNA duplexes containing single adenosine (5′GUCGAGCUG-3′/5′-CAGCCGAC-3′) and uridine bulge (5′-GUCGUGCUG-3′/5′CAGCCGAC-3′) have been studied using NMR spectroscopy and in aqua simulation of molecular dynamics. In both NMR structures, the bulged residues are oriented toward the minor groove. The bulged adenosine participates in the base triple formation being coplanar with the 5′neighboring residue G4 which pairs with cytidine C14 from the opposite strand. The uridine bulge adopts a looped-out conformation pointing toward the residue G15 and bridges the minor groove to 5′ side of the helix. NMR-derived structures have been used to formulate the initial RNA duplex models for the MD simulation. Results of molecular dynamics simulations in explicit solvent support the conclusion concerning the formation of a dinucleotide platform within the C:G-A triple. As suggested by NMR results, the uridine bulge shows considerable dynamics.