Structural features and stability of an RNA triple helix in solution

Structural features and stability of an RNA triple helix in solution
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DOI:
10.1093/nar/24.14.2841
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发表时间:
1996-07-15
影响因子:
14.9
通讯作者:
Hoffman, DW
Hoffman, DW
中科院分区:
生物学2区
文献类型:
--
作者:
Holland, JA;Hoffman, DW

文献摘要

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通过一维和二维NMR光谱和紫外吸收测量值分析了具有序列序列的30 NT RNA,该序列分析了分子内三重螺旋,NMR数据表明,RNA含有七个吡啶胺 - 吡啶胺 - 吡啶 - 吡啶胺基碱基,该基因由Watson-Crick稳定在和Hoogsteen互动。伊米诺质子共振的温度依赖性以及紫外线吸收数据表明,三重螺旋在酸性pH值下高度稳定,在pH 4.3时在62摄氏度的单个尖锐过渡中熔化。 Watson-Crick和Hoogsteen配对在融化时同时被破坏。 NMR数据与watson-Crick配对链形成A螺旋的结构模型一致。在NMR数据的指导下,模型构建的结果表明,Hoogsteen链的2'羟基质子与嘌呤链的磷酸氧之间可能存在氢键。讨论了结构模型,以说明RNA和DNA三重螺旋报告的稳定性差异的能力,并提供了对可能在RNA结合化合物设计中很重要的特征的见解。
A 30 nt RNA with a sequence designed to form an intramolecular triple helix was analyzed by one- and two-dimensional NMR spectroscopy and UV absorption measurements, NMR data show that the RNA contains seven pyrimidine-purine-pyrimidine base triples stabilized by Watson-Crick and Hoogsteen interactions. The temperature dependence of the imino proton resonances, as well as UV absorption data, indicate that the triple helix is highly stable at acidic pH, melting in a single sharp transition centered at 62 degrees C at pH 4.3. The Watson-Crick and Hoogsteen pairings are disrupted simultaneously upon melting. The NMR data are consistent with a structural model where the Watson-Crick paired strands form an A-helix. Results of model building, guided by NMR data, suggest a possible hydrogen bond between the 2' hydroxyl proton of the Hoogsteen strand and a phosphate oxygen of the purine strand. The structural model is discussed in terms of its ability to account for some of the differences in stability reported for RNA and DNA triple helices and provides insight into features that are likely to be important in the design of RNA binding compounds.