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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引用次数: 0
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.
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.