Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
Biochemistry. 2011 Aug 23;50(33):7251-8. doi: 10.1021/bi200805j. Epub 2011 Jul 11.
G-Quadruplexes are noncanonical nucleic acid secondary structures based on guanine association that are readily adopted by G-rich RNA and DNA sequences. Naturally occurring genomic G-quadruplex-forming sequences have functional roles in biology that are mediated through structure. To appreciate how this is achieved, an understanding of the likelihood of G-quadruplex formation and the structural features of the folded species under a defined set of conditions is informative. We previously systematically investigated the thermodynamic stability and folding topology of DNA G-quadruplexes and found a strong dependence of these properties on loop length and loop arrangement [Bugaut, A., and Balasubramanian, S. (2008) Biochemistry 47, 689-697]. Here we report on a complementary analysis of RNA G-quadruplexes using UV melting and circular dichroism spectroscopy that also serves as a comparison to the equivalent DNA G-quadruplex-forming sequences. We found that the thermodynamic stability of G-quadruplex RNA can be modulated by loop length while the overall structure is largely unaffected. The systematic design of our study also revealed subtle loop length dependencies in RNA G-quadruplex structure.
四链体是基于鸟嘌呤结合的非经典核酸二级结构，容易被富含鸟嘌呤的 RNA 和 DNA 序列采用。天然存在的基因组形成四链体的序列在生物学中具有功能作用，这些作用是通过结构介导的。为了理解这是如何实现的，了解四链体形成的可能性以及在一组定义条件下折叠物种的结构特征是有帮助的。我们之前系统地研究了 DNA 四链体的热力学稳定性和折叠拓扑结构，发现这些性质强烈依赖于环长和环排列[Bugaut，A.，和 Balasubramanian，S.（2008）生物化学 47，689-697]。在这里，我们使用紫外熔融和圆二色性光谱法报告了 RNA 四链体的互补分析，这也可作为与等效的 DNA 形成四链体的序列的比较。我们发现，四链体 RNA 的热力学稳定性可以通过环长来调节，而整体结构则基本不受影响。我们研究的系统设计还揭示了 RNA 四链体结构中微妙的环长依赖性。
