The solution structure of a dimethylenesulfone-linked analogue of the RNA dimer UpC was determined using two-dimensional NMR and restrained molecular dynamics. In CDCl3, the RNA analogue forms a parallel duplex with a single U:U base pair and roughly antiparallel orientation of the two ribose rings within each strand. A hydrogen bonding network stabilizing this duplex was indirectly deduced from the NMR data. Besides the two-pronged hydrogen bonding between the uridines, this network includes two hydrogen bonds from the ribose hydroxyls of one strand to O2 of the cytosine bases of the opposite strand, and intrastrand hydrogen bonds from the 2＇ hydroxyls of the 5＇-terminal residues to hydroxyls of the 3＇-terminal residue. The melting point of the duplex determined via NMR chemical shift analysis was found to be 91 degrees C for a 11 mM solution in 1,1,2,2-tetrachloroethane-d(2). Based on van＇t Hoff analysis of the available UV melting data in 1,2-dichloroethane, duplex formation is associated with a Delta S degrees of -47 cal K-1 mol(-1) and a Delta H degrees of -22 kcal mol(-1). The observation that an RNA analogue rendered nonionic and removed from an aqueous environment forms an exceptionally stable non-Watson-Crick duplex with backbone-to-nucleobase and backbone-to-backbone hydrogen bonds suggests that a charged backbone and the solubility in aqueous medium that it conveys are important for limiting the repertoire of strand-strand interactions of oligoribonucleotides.