The structure of an RNA dodecamer shows how tandem U-U base pairs increase the range of stable RNA structures and the diversity of recognition sites

Background: Non-canonical base pairs are fundamental building blocks of RNA structures. They can adopt geometries quite different from those of canonical base pairs and are common in RNA molecules that do not transfer sequence information, Tandem U-U base pairs occur frequently, and can stabilize duplex formation despite the fact that a single U-U base pair is destabilizing. Results: We determined the crystal structure of the RNA dodecamer GGCGCUUGCGUC at 2.4 Angstrom resolution. The molecule forms a duplex containing tandem U-U base pairs, which introduce an overall bend of 11-12 degrees in the duplex resulting from conformational changes at each interface between the tandem U-U base pairs and a flanking duplex sequence, The formation of the U-U base pairs cause small changes in several backbone torsion angles; base stacking is preserved and two hydrogen bonds are formed per base pair, explaining the stability of the structure. Conclusions: Tandem U-U base pairs can produce stable structures not accessible to normal A-form RNA, which may allow the formation of specific interfaces for RNA-RNA or RNA-protein recognition. These base-pairs show an unusual pattern of hydrogen-bond donors and accepters in the major and minor grooves, which could also act as a recognition site.