Stability Factors of the Parallel Quadruplexes: DNA Versus RNA

One of the most stable quadruplexes is formed by the 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 analogue, 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). Although the 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, whereas the chain-reversal loops play an important role in higher stability of RNA quadruplexes. In addition, we have shown that the 5'-end of RNA quadruplexes represents a 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.