Stability Factors of the Parallel Quadruplexes: DNA vs RNA.

One of the most stable quadruplexes is formed by G3T sequence (GGGTGGGTGGGTGGG) that folds into a parallel quadruplex with three G-tetrads and chain-reversal T-loops. For example, in 1 mM K+ it unfolds at 75 °C and at physiological conditions it unfolds above 100 °C. The RNA analog, ggguggguggguggg (g3u), which employs exactly same folding topology, demonstrates even higher thermal stability. Here, we performed melting experiments of G3T, g3u and more than 30 chimeric constructs (G3T with RNA nucleotides at certain positions). While g3u quadruplex is 13 °C more stable than G3T, majority of G®g (DNA-for-RNA) substitutions destabilize G3T. Only three G®g and loop T®u substitutions stabilize the structure. However, stabilization effects of these six substitutions overcome destabilization of other nine G®g resulting in higher stability of all-RNA g3u. The present work clearly indicates that the stacking interactions are more favorable in parallel DNA quadruplexes, while the chain-reversal loops play important role in higher stability of RNA quadruplexes. In addition, we have shown that 5'-end of RNA quadruplexes represents more favorable target for stacking interactions than the 3'-end. Based on the current study, rational design of the quadruplexes for particular biotechnological applications and drugs, targeting the quadruplexes, may be envisaged.