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NMR Study on Nucleic Acids

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Handbook of Chemical Biology of Nucleic Acids

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Abstract

Nucleic acid structures and their interactions with cellular constituents continue to offer surprises despite decades of structural, biophysical, and biochemical studies. Knowledge of the structure and dynamics of nucleic acids is important not only for understanding biological mechanisms, but also for developing new therapeutics. NMR (Nuclear Magnetic Resonance) spectroscopy has been used for many years to determine the structure of nucleic acids as well as their dynamics and interactions with proteins, other nucleic acids, low molecular weight ligands, cations, and solvent molecules. Recent studies use nucleic acids to create new materials or focus on the interactions of small molecule ligands with large entities such as the ribosome, while novel in vivo methods enable probing of RNA structure and proteins that remodel nucleic acid structures, correct for chemical damage to DNA, modulate gene expression by binding to RNAs, etc. 1H NMR experiments allow determination of NOE effects and scalar coupling constants between nearby protons of nucleobases and sugar units. The low proton density of nucleic acids allows for rapid detection and identification of hydrogen bonds, which enable assessment of folding and provide constraints for defining base pair arrangements and assessing secondary structure. Sequential resonance assignment is typically followed by collection of structural restraints and structure determination at high resolution. Conventionally, the structure determination process is based on interpretation of magnetization transfer between protons through space mediated by carbon, nitrogen, and phosphorus atoms. Numerous advances including the introduction of ingenious pulse sequences and refined sample preparation strategies have enabled NMR structure determination of RNAs larger than 100-nt. These advances, coupled with improved workflows that incorporate hybrid methods of structure determination, have pushed the boundaries for studying larger, more complex, and biologically relevant systems into new dimensions. With multidimensional NMR experiments, we can measure the dynamics of constituent nuclei along the entire DNA and RNA structure and characterize functionally important motions that range from picoseconds to seconds and longer.

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Acknowledgments

The author is grateful to the colleagues named in the cited papers from his laboratory at Slovenian NMR center, especially Drs. Trajkovski, Šket, Lenarčič Živković, Kocman, Kotar, Marušič, Podbevšek, Pavc, Toplishek, and Cevec. The help of Klemen Pečnik, Dr. Marko Trajkovski, Matic Kovačič, and Dr. Primož Šket in the preparation of the artwork is gratefully acknowledged. This work was supported partly by the Slovenian Research Agency (ARRS, grants P1-0242 and J1-1704).

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  1. Slovenian NMR Centre, National Institute of Chemistry, Ljubljana, Slovenia

    Janez Plavec

  2. Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia

    Janez Plavec

  3. EN-FIST Center of Excellence, Ljubljana, Slovenia

    Janez Plavec

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  1. Janez Plavec
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Correspondence to Janez Plavec .

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Editors and Affiliations

  1. Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University, Kobe, Japan

    Naoki Sugimoto

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  1. Slovenian NMR Centre, National Institute of Chemistry, Ljubljana, Slovenia

    Janez Plavec

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Plavec, J. (2022). NMR Study on Nucleic Acids. In: Sugimoto, N. (eds) Handbook of Chemical Biology of Nucleic Acids. Springer, Singapore. https://doi.org/10.1007/978-981-16-1313-5_8-1

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  • DOI: https://doi.org/10.1007/978-981-16-1313-5_8-1

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