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首页> 外文期刊>Nucleic Acids Research >Distinctive structural motifs of RNA G-quadruplexes composed of AGG, CGG and UGG trinucleotide repeats
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Distinctive structural motifs of RNA G-quadruplexes composed of AGG, CGG and UGG trinucleotide repeats

机译：由AGG，CGG和UGG三核苷酸重复序列组成的RNA G四联体的独特结构基序

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摘要

Trinucleotide repeats are microsatellite sequences that are polymorphic in length. Their expansion in specific genes underlies a number of neurodegenerative disorders. Using ultraviolet-visible, circular dichroism, nuclear magnetic resonance (NMR) spectroscopies and electrospray ionization mass spectrometry, the structural preferences of RNA molecules composed of two and four repeats of AGG, CGG and UGG in the presence of K+, Na+ and NH4+ were analysed. (AGG)(2)A, (AGG)(4)A, p(UGG)(2)U and p(UGG)(4)U strongly prefer folding into G-quadruplexes, whereas CGG-containing sequences can adopt different types of structure depending on the cation and on the number of repeats. In particular, the two-repeat CGG sequence folds into a G-quadruplex in potassium buffer. We also found that each G-quadruplex fold is different: A:(G:G:G:G)A hexads were found for (AGG)(2)A, whereas mixed G: C: G: C tetrads and U-tetrads were observed in the NMR spectra of G(CGG)(2)C and p(UGG)(2)U, respectively. Finally, our NMR study highlights the influence of the strand sequence on the structure formed, and the influence of the intracellular environment on the folding. Importantly, we highlight that although potassium ions are prevalent in cells, the structures observed in the HeLa cell extract are not always the same as those prevailing in biophysical studies in the presence of K+ ions.
机译：三核苷酸重复序列是长度多态的微卫星序列。它们在特定基因中的扩增是许多神经退行性疾病的基础。使用紫外可见圆二色性，核磁共振（NMR）光谱和电喷雾电离质谱法，分析了在K +，Na +和NH4 +存在下由AGG，CGG和UGG的两个和四个重复序列组成的RNA分子的结构偏好。 。 （AGG）（2）A，（AGG）（4）A，p（UGG）（2）U和p（UGG）（4）U非常喜欢折叠成G-四链体，而包含CGG的序列可以采用不同的类型取决于阳离子和重复次数的结构。特别地，两个重复的CGG序列在钾缓冲液中折叠成G-四链体。我们还发现每个G-四倍体折叠是不同的：（AGG）（2）A发现A：（G：G：G：G）A六角，而G：C：G：C四联和U-四联分别在G（CGG）（2）C和p（UGG）（2）U的NMR光谱中观察到。最后，我们的NMR研究强调了链序列对形成的结构的影响以及细胞内环境对折叠的影响。重要的是，我们强调尽管钾离子在细胞中很普遍，但在HeLa细胞提取物中观察到的结构并不总是与存在K +离子的生物物理研究中普遍存在的结构相同。

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