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 o f RNA structures. They can adopt geometries quite different from those of canonical base pairs and are common in RNA molecules that do not t ransfer 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 structu re of the RNA dodecamer GGCGCUUGCGUC at 2.4 Angstrom resolution. The m olecule forms a duplex containing tandem U-U base pairs, which introdu ce an overall bend of 11-12 degrees in the duplex resulting from confo rmational changes at each interface between the tandem U-U base pairs and a flanking duplex sequence, The formation of the U-U base pairs ca use 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 ca n produce stable structures not accessible to normal A-form RNA, which may allow the formation of specific interfaces for RNA-RNA or RNA-pro tein 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.