Nearest neighbor parameters for Inosine•Uridine pairs in RNA duplexes

An enzyme family known as adenosine deaminases that act on RNA (ADARs) catalyzes adenosine deamination in RNA. ADARs act on RNA that is largely double-stranded and convert adenosine to inosine, resulting, in many cases, in an I center dot U pair. Thermodynamic parameters derived from optical melting studies are reported for a series of 14 oligoribonucleotides containing single I center dot U pairs adjacent to Watson-Crick pairs. In order to determine unique linearly independent nearest neighbor parameters for I center dot U pairs, four duplexes containing 3'-terminal I center dot U pairs and four duplexes containing 5'-terminal I center dot U pairs have also been thermodynamically characterized. This data was combined with previously published data of seven duplexes containing internal, terminal, or tandem I center dot U pairs from Strobel et al. [Strobel, S. A., Cech, T. R., Usman, N., and Beigelman, L. (1994) Biochemistry 33, 13824-13838] and Serra et al. [Serra, M. J., Smolter, P. E., and Westhof, E. (2004) Nucleic Acids Res. 32, 1824-1828]. On average, a duplex with an internal I center dot U pair is 2.3 kcal/mol less stable than the same duplex with an A-U pair, however, a duplex with a terminal I center dot U pair is 0.8 kcal/mol more stable than the same duplex with an A-U pair. Although isosteric with a G-U pair, on average, a duplex with an internal I center dot U pair is 1.9 kcal/mol less stable than the same duplex with a G-U pair, however, a duplex with a terminal I center dot U pair is 0.9 kcal/mol more stable than the same duplex with a G-U pair. Duplexes with tandem I center dot U pairs are on average 5.9 and 3.8 kcal/mol less stable than the same duplex with tandem A-U or tandem G-U pairs, respectively. Using the combined thermodynamic data and a complete linear least-squares fitting routine, nearest neighbor parameters for all nearest neighbor combinations of I center dot U pairs and an additional parameter for terminal I center dot U pairs have been derived.