Nearest neighbor parameters for inosine x 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 x U pair. Thermodynamic parameters derived from optical melting studies are reported for a series of 14 oligoribonucleotides containing single I x U pairs adjacent to Watson-Crick pairs. In order to determine unique linearly independent nearest neighbor parameters for I x U pairs, four duplexes containing 3'-terminal I x U pairs and four duplexes containing 5'-terminal I x U pairs have also been thermodynamically characterized. This data was combined with previously published data of seven duplexes containing internal, terminal, or tandem I x 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 x 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 x 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 x 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 x U pair is 0.9 kcal/mol more stable than the same duplex with a G-U pair. Duplexes with tandem I x 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 x U pairs and an additional parameter for terminal I x U pairs have been derived.
Wright
Daniel J
DJ
Department of Chemistry, Saint Louis University, Saint Louis, Missouri 63103, USA.
Rice
Jamie L
JL
Yanker
Dawn M
DM
Znosko
Brent M
BM
D000241:Adenosine / Q000737:chemistry; D000465:Algorithms; D020029:Base Pairing; D001483:Base Sequence; D006151:Guanosine / Q000737:chemistry; D007288:Inosine / Q000737:chemistry*; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009692:Nucleic Acid Heteroduplexes / Q000737:chemistry*; D012313:RNA / Q000138:chemical synthesis / Q000737:chemistry*; D013816:Thermodynamics; D014529:Uridine / Q000737:chemistry*
D009692:Nucleic Acid Heteroduplexes; D006151:Guanosine; D007288:Inosine; D012313:RNA; D000241:Adenosine; D014529:Uridine