Double-stranded RNA bending by AU-tract sequences

Alberto Marin-Gonzalez, Clara Aicart-Ramos, Mikel Marin-Baquero, Alejandro Martín-González, Maarit Suomalainen, Abhilash Kannan, J. G. Vilhena, Urs F. Greber, Fernando Moreno-Herrero and Rubén Pérez.

Abstract: Sequence-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.

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