Double-stranded RNA bending by AU-tract sequences

Abstract

ABSTRACTSequence-dependent structural deformations of the DNA double helix (dsDNA) have been extensively studied, where adenine tracts (A-tracts) provide a striking example for global bending in the molecule. In contrast to dsDNA, much less is known about how the nucleotide sequence affects bending deformations of double-stranded RNA (dsRNA). Using all-atom microsecond long molecular dynamics simulations we found a sequence motif consisting of alternating adenines and uracils, or AU-tracts, that bend the dsRNA helix by locally compressing the major groove. We experimentally tested this prediction using atomic force microscopy (AFM) imaging of long dsRNA molecules containing phased AU-tracts. AFM images revealed a clear intrinsic bend in these AU-tracts molecules, as quantified by a significantly lower persistence length compared to dsRNA molecules of arbitrary sequence. The bent structure of AU-tracts here described might play a role in sequence-specific recognition of dsRNAs by dsRNA-interacting proteins or impact the folding of RNA into intricate tertiary and quaternary structures.