Visualizing Disordered Single-Stranded RNA: Connecting Sequence, Structure, and Electrostatics

Disordered homopolymeric regions of single-stranded RNA, such as U or A tracts, are found within functional RNAs where they play distinct roles in defining molecular structure and facilitating recognition by partners. Despite this prominence, details of conformational and biophysical properties of these regions have not yet been resolved. We apply a number of experimental techniques to investigate the conformations of these biologically important motifs and provide quantitative measurements of their ion atmospheres. Single strands of RNA display pronounced sequence-dependent conformations that relate to the unique ion atmospheres each attracts. Chains of rU bases are relatively unstructured under all conditions, while chains of rA bases display distinct ordering through stacking or clustering motifs, depending on the composition of the surrounding solution. These dramatic structural differences are consistent with the measured disparity in ion composition and atmospheres around each homopolymer, revealing a complex interplay of base, ion, and single-strand ordering. The unique structural and ionic signatures of homopolymer ssRNAs explains their role(s) in folding structured RNAs and may explain their distinct recognition by protein partners.