CONFORMATIONAL PROPERTIES AND THERMODYNAMICS OF THE RNA DUPLEX R(CGCAAAUUUGCG)(2) - COMPARISON WITH THE DNA ANALOG D(CGCAAATTTGCG)(2)

The thermodynamic stability of nine dodecamers (four DNA and five RNA) of the same base composition has been compared by UV-melting, The Del ta G of stabilisation were in the Order: r(GACUGAUCAGUC)(2) > r(CGCAAA TTTGCG)(2) approximate to r(CGCAUAUAUGCG)(2) > d(CGCAAATTTGCG)(2) appr oximate to r(CGCAAAUUUGCG)(2) > d(CGCATATATGCG)(2) approximate to d(GA CTGATCAGTC)(2) > r(CGCUUUAAAGCG)(2) approximate to d(CGCATATATGCG)(2). Compared with the mixed sequences, both r(AAAUUU) and r(UUUAAA) are g reatly destablising in RNA, whereas in DNA, d(TTTAAA) is destabilising but d(AAATTT) is stabilising, which has been attributed to the format ion of a special B' structure involving large propeller twists of the A-T base pairs, The solution structure of the RNA dodecamer r(CGCAAAUU UGCG)(2) has been determined using NMR and restrained molecular dynami cs calculations to assess the conformational reasons for its stability in comparison with d(CGCAAATTTGCG)(2). The structures refined to a me an pairwise r.m.s.d. of 0.89 +/- 0.29 Angstrom. The nucleotide conform ations are typical of the A family of structures, However, although th e helix axis displacement is similar to 4.6 Angstrom into the major gr oove, the rise(3.0 Angstrom) and base inclination (similar to 6 degree s) are different from standard A form RNA, The extensive base-stacking found in the AAATTT tract of the DNA homologue that is largely respon sible for the higher thermodynamic stability of the DNA duplex is redu ced in the RNA structure, which may account for its low relative stabi lity.