Monomorphic RNA G-Quadruplex and Polymorphic DNA G-Quadruplex Structures Responding to Cellular Environmental Factors

摘要

We systematically and quantitatively investigated the structure and thermodynamics ofnG-quadruplexes of RNAs and corresponding DNAs of the same sequences under molecular crowdingnconditions that mimic the high osmotic stress induced by the numerous molecules inside of living cells.nStructural analyses demonstrated that various telomere RNA sequences folded into parallel-strandednG-quadruplexes in a manner independent of the surrounding conditions with different cations under bothndilute and molecular crowding conditions. In contrast, DNA G-quadruplexes showed structural polymorph-nism.Moreover, we demonstrated that theG-quadruplexes of the RNA sequences weremore stable than thosenof the same DNA sequences. These results show that a single and robust RNA G-quadruplex structure cannexist in a manner independent of the sequence and surrounding conditions. To confirm this, we studied anguanine-rich sequence located in the 50n-untranslated region of human bcl-2 mRNA that is thought to play anrole in translation. The results revealed a stable parallelG-quadruplex that formed under all conditions tested.nFor example, a bcl-RNA G-quadruplex in the presence of 5 mM KCl [free energy change at 25 u0001C(ΔGu000125)nof -5.42 kcal/mol] was more stable than its corresponding DNA G-quadruplex (ΔGu000125 = -2.31 kcal/mol).nOur results further indicated that watermolecules binding to the 20n-OHgroup ofRNAG-quadruplexes play ancritical role in their formation and stability.