STRUCTURE OF A MISPAIRED RNA DOUBLE HELIX AT 1.6-A RESOLUTION AND IMPLICATIONS FOR THE PREDICTION OF RNA SECONDARY STRUCTURE

The nonamer r(GCUUCGGC)d(Br)U, where d(Br)U is 5-bromo-2'-deoxyuridine , contains the tetraloop sequence UUCG. It crystallizes in the presenc e of Rh(NH3)(6)Cl-3. In solution the oligomer is expected to form a ha irpin loop but the x-ray structure analysis, to a resolution of 1.6 An gstrom, indicates an eight-base-pair A-RNA duplex containing a central block of two G.U and two C.U pairs. Self-pairs which approximate to W atson-Crick geometry are also formed in the extended crystal structure between symmetry-related U-Br residues and are part of infinite doubl e-helical stacks. The G.U pair is a wobble base pair analogous to the G.T pair found in DNA fragments. The C.U mismatch involves one hydroge n-bonded contact between the bases and a bridging water molecule which ensures a good fit of the base pair in the RNA helix. The U-Br.U-Br p air is held by two hydrogen bonds in an orientation which is compatibl e with duplex geometry. The structure observed within the crystal has some parallels with the structure of globular RNAs, and the presence o f stable, noncanonical base pairs has implications for the prediction of RNA secondary structure.