Crystal structure of an RNA double helix incorporating a track of non-Watson–Crick base pairs

Abstract

THE crystal structure of the RNA dodecamer duplex (r-GGACUUCGGUCC)₂ has been determined. The dodecamers stack end-to-end in the crystal, simulating infinite A-form helices with only a break in the phosphodiester chain. These infinite helices are held together in the crystal by hydrogen bonding between ribose hydroxyl groups and a variety of donors and acceptors. The four noncomplementary nucleotides in the middle of the sequence did not form an internal loop, but rather a highly regular double-helix incorporating the non-Watson–Crick base pairs, G · U and U · C. This is the first direct observation of a U · C (or T · C) base pair in a crystal structure. The U · C pairs each form only a single base–base hydrogen bond, but are stabilized by a water molecule which bridges between the ring nitrogens and by four waters in the major groove which link the bases and phosphates. The lack of distortion introduced in the double helix by the U · C mismatch may explain its low efficiency of repair in DNA. The G · U wobble pair is also stabilized by a minor-groove water which bridges between the unpaired guanine amino and the ribose hydroxyl of the uracil. This structure emphasizes the importance of specific hydrogen bonding between not only the nucleotide bases, but also the ribose hydroxyls, phosphate oxygens and tightly bound waters in stabilization of the intramolecular and intermolecular structures of double helical RNA.