SYMMETRY AND STRUCTURE OF RNA AND DNA TRIPLE HELICES

Despite wide interest in nucleic acid triple helices, there has been n o stereochemically satisfactory structure of an RNA triple helix in at omic detail. An RNA triplex structure has previously been proposed bas ed on fiber diffraction and molecular modeling [S. Arnott and P.J. Bon d (1973) Nature New Biology, Vol. 244, pp. 99-101; S. Arnott, P.J. Bon d, E. Selsing, and P.J.C. Smith (1976) Nucleic Acids Research, Vol. 3, pp. 2459-2470], but it has not nonallowed close contacts at every tri plet and is therefore not stereochemically acceptable. We propose here a new model fro an RNA triple helix in which the three chains have id entical backbone conformations and are symmetry related. There are no short contacts. The modeling employs a novel geometrical approach usin g the linked atom least squares [P.J.C. Smith and S. Arnott (1978) Act a Crystallographica, Vol A34, pp. 3-11] program and is not based on en ergy minimization. In general, the method leads to a rang of possible structures rather than a unique structure. In the present case, howeve r, the constraints resulting from the introduction of a third strand l imit the possible structures to a very small range of conformation spa ce. This method was used previously to obtain a model for DNA triple h elices [G. Raghunathan, H.T. Miles, and V. Sasisekharan (1993) Biochem istry, Vol. 32, pp. 455-462], subsequently confirmed by fiber-type x-r ay diffraction of oligomeric crystals [K. Liu, H.T. Miles, K.D. Parris , and V. Sasisekharan (1994) Nature Structural Biology, Vol. 1, pp. 11 -12]. The above triple helices have Watson-Crick-Hoogsteen [K. Hoogste en (1963) Acta Crystallographica, Vol. 16, pp. 907-916] pairing of the three bases. The same modeling method was used to investigate the fea sibility of three-dimensional structures based on the three possible a lternative hydrogen-bonding schemes: Watson-Crick-reverse Hoogsteen, D onohue [J. Donohue (1953) Proceedings of the National Academy of Scien ce USA, Vol. 39, pp. 470-475] (reverse Watson-Crick)-Hoogsteen, and Do nohue-reverse Hoogsteen. We found that none of these can occur in eith er RNA or DNA helices because they give rise only to structures with p rohibitively short contacts between backbone and base atoms in the sam e chain. (C) 1995 John Wiley and Sons, Inc.