Balaratnam Sumirtha, Basu Soumitra
Department of Chemistry and Biochemistry, Kent State University, Kent, OH, 44242.
Biopolymers. 2015 Jul;103(7):376-86. doi: 10.1002/bip.22628.
DNA and RNA sequences rich in guanosines (G) can form a four-stranded secondary structure known as a G-quadruplex (GQ), which plays a role in regulation of gene expression at the transcription and translation level. Both DNA and RNA GQs typically use the monovalent K(+) ion for stabilization of the structures. However, the fundamental reasons for K(+) acting as the most stabilizing metal ion for RNA GQs are not known. To identify the properties of a metal ion that stabilizes an RNA GQ we investigated the effect of alkaline earth metal cations and a set of divalent transition metal ions on two previously identified highly stable RNA GQs. Our results based upon circular dichroism and RNase T1 structure mapping data reveal that the RNA GQs are destabilized in the presence of the tested divalent metal cations. The destabilizing effect of a divalent metal cation is reversible upon increasing K(+) concentration. Results show that ionic radius, hydration energy, and binding strength towards the hard ligand (guanine O(6)) are important factors that determine a metal ion's ability to stabilize an RNA GQ. Additionally, the tested set of divalent metal cations incongruously affects RNA and DNA GQs.
富含鸟苷（G）的DNA和RNA序列可形成一种称为G-四链体（GQ）的四链二级结构，其在转录和翻译水平的基因表达调控中发挥作用。DNA和RNA GQ通常都使用单价K(+)离子来稳定结构。然而，K(+)作为RNA GQ最稳定的金属离子的根本原因尚不清楚。为了确定稳定RNA GQ的金属离子的特性，我们研究了碱土金属阳离子和一组二价过渡金属离子对两个先前鉴定出的高度稳定的RNA GQ的影响。我们基于圆二色性和核糖核酸酶T1结构图谱数据的结果表明，在测试的二价金属阳离子存在下，RNA GQ会变得不稳定。增加K(+)浓度后，二价金属阳离子的去稳定作用是可逆的。结果表明，离子半径、水合能以及对硬配体（鸟嘌呤O(6)）的结合强度是决定金属离子稳定RNA GQ能力的重要因素。此外，测试的二价金属阳离子组对RNA和DNA GQ的影响不一致。
