The oligonucleotides containing N7-regioisomer of guanosine. Influence on thermodynamic properties and structure of RNA duplexes.

IF 4.2 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY RNA Pub Date : 2024-10-28 DOI:10.1261/rna.080106.124
Aleksandra Jarmolowicz, Nivedita Dutta, Witold Andralojc, Joanna Sarzynska, Grzegorz Framski, Daniel Baranowski, Jerzy Boryski, Ansuman Lahiri, Zofia Gdaniec, Elzbieta Kierzek, Ryszard Kierzek
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Abstract

During chemical synthesis of the purine riboside, the N7-regioisomer is kinetically formed whereas the N9-regioisomer is a thermodynamically formed product. We have studied the effect of substituting the N9-regioisomer of guanosine with its N7-regioisomer (N7-guanosine, 7G) at a central position of several RNA duplexes. We found that this single substitution by 7G severely diminished their thermodynamic stabilities when 7G paired with C and U, but remarkably, led to a significant amount of stabilization in most of the duplexes when forming mismatches with G and A. The extent of stabilization was observed to be dependent on the sequence and orientation of neighboring base pairs of N7-guanosine. 1D and 2D NMR studies on the duplexes along with extensive molecular dynamics simulations revealed the conformational differences occurring due to substitution of G by 7G and it was observed that the thermodynamic results were largely explainable by considering the formation of stable non-canonical hydrogen bonding interactions, although other interactions such as stacking and electrostatic interactions could also play a role. These observations can have important applications in the design of RNA-based disease diagnostics and therapeutics.

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含有鸟苷 N7-regioisomer 的寡核苷酸。对 RNA 双链体热力学性质和结构的影响。
在嘌呤核苷的化学合成过程中,N7-杂环异构体是动力学形成的,而 N9-杂环异构体则是热力学形成的产物。我们研究了在几个 RNA 双链的中心位置用鸟苷的 N7-regioisomer (N7-鸟苷,7G)取代鸟苷的 N9-regioisomer 的效果。我们发现,当 7G 与 C 和 U 配对时,7G 的单次取代会严重降低它们的热力学稳定性,但值得注意的是,当 7G 与 G 和 A 形成错配时,大多数双链体的稳定性会显著提高。对双链体进行的一维和二维核磁共振研究以及广泛的分子动力学模拟揭示了由于 G 被 7G 取代而产生的构象差异,并观察到热力学结果在很大程度上可以通过考虑形成稳定的非经典氢键相互作用来解释,尽管其他相互作用(如堆积和静电相互作用)也可能发挥作用。这些观察结果可在设计基于 RNA 的疾病诊断和治疗中得到重要应用。
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来源期刊
RNA
RNA 生物-生化与分子生物学
CiteScore
8.30
自引率
2.20%
发文量
101
审稿时长
2.6 months
期刊介绍: RNA is a monthly journal which provides rapid publication of significant original research in all areas of RNA structure and function in eukaryotic, prokaryotic, and viral systems. It covers a broad range of subjects in RNA research, including: structural analysis by biochemical or biophysical means; mRNA structure, function and biogenesis; alternative processing: cis-acting elements and trans-acting factors; ribosome structure and function; translational control; RNA catalysis; tRNA structure, function, biogenesis and identity; RNA editing; rRNA structure, function and biogenesis; RNA transport and localization; regulatory RNAs; large and small RNP structure, function and biogenesis; viral RNA metabolism; RNA stability and turnover; in vitro evolution; and RNA chemistry.
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