Stability prediction of canonical and non-canonical structures of nucleic acids in various molecular environments and cells

Nucleic acids (DNA and RNA) dynamically fold and unfold to exert their functions in cells. These folding and unfolding behaviours are also the basis for various technical applications. To understand the biological mechanism of nucleic acid function, and design active materials using nucleic acids, b...

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Published inChemical Society reviews Vol. 49; no. 23; pp. 8439 - 8468
Main Authors Takahashi, Shuntaro, Sugimoto, Naoki
Format Journal Article
LanguageEnglish
Published London Royal Society of Chemistry 07.12.2020
Subjects
Acids
Crowding
Deoxyribonucleic acid
DNA
Gene expression
Nucleic acids
Predictions
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Summary:Nucleic acids (DNA and RNA) dynamically fold and unfold to exert their functions in cells. These folding and unfolding behaviours are also the basis for various technical applications. To understand the biological mechanism of nucleic acid function, and design active materials using nucleic acids, biophysical approaches based on thermodynamics are very useful. Methods for predicting the stability of canonical duplexes of nucleic acids have been extensively investigated for more than half a century and are now widely used. However, such predictions are not always accurate under various solution conditions, particularly cellular conditions, as the concentrations of cations and cosolutes under intracellular conditions, named as molecular crowding, differ from those under standard experimental conditions. Moreover, the crowding condition in cells is spatiotemporally variable. Furthermore, non-canonical structures such as triplex and tetraplex exist in cells and play important roles in gene expression. Therefore, a prediction method reflecting the cellular conditions must be established to determine the stability of various nuclei acid structures. This article reviews the biophysicochemical background of predicting nucleic acid stability and recent advances in the prediction of this stability under cellular conditions. This review provides the biophysicochemical background and recent advances in stability prediction of canonical and non-canonical structures of nucleic acids in various molecular environments and cells.
Bibliography:Shuntaro Takahashi is an Associate Professor at the Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University. Dr Takahashi earned his PhD degree in Tokyo Institute of Technology, Japan in 2007. After a period of research at Tokyo Institute of Technology as an Assistant Professor, he joined FIBER in 2012. He is currently studying the biophysics of nucleic acids in cells and the mechanism of molecular crowding for nucleic acid structures that affect cellular metabolism.
Professor Sugimoto received his PhD in 1985 from Kyoto University, Japan. After completing his postdoctoral work at the University of Rochester in the USA, he became a faculty member at Konan University in Kobe, Japan in 1988. He has been a full professor since 1994 and a director at the Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University since 2003. He received The Imbach-Townsend Award from IS3NA in 2018. In 2020, he was awarded CSJ Awards from the Chemical Society of Japan. His research interests include biophysical chemistry, biomaterials, biofunctional chemistry, and biotechnology in the field of nucleic acid chemistry.
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ISSN:0306-0012
1460-4744
DOI:10.1039/d0cs00594k