Biomolecular NMR Spectroscopy of Ribonucleic Acids

Biomolecular nuclear magnetic resonance (NMR) spectroscopy allows the characterisation of structural and dynamic properties of ribonucleic acids (RNAs) in solution. The NMR-based determination of high-resolution three-dimensional (3D) structures by NMR spectroscopy in solution is especially useful for small-to-medium sized RNA molecules like aptamers and small ribozymes, but has also been achieved for RNAs up to about 100 nucleotides in total size. Biomolecular NMR also provides valuable information about the interaction between RNA and diverse binding partners such as drugs, peptides, proteins or other nucleic acids. In addition, novel methods can be utilised to characterise the role of metal ions, intramolecular dynamics across a range of motion time scales and shifted pKa values of exchangeable nucleobase protons in RNA structure and catalysis. Key Concepts: High-resolution NMR spectroscopy in solution is a powerful method to determine the 3D structures of small and medium sized RNA molecule. The structure determination of larger RNAs generally requires labelling with stable isotopes The information about molecular dynamics that can be obtained by NMR experiments allows quantitative studies of molecular motion across a wide range of time scales. The possibility to directly observe changes in the pKa values of ionisable groups. The localisation of divalent metal ions can be defined using several NMR methods. Keywords: RNA structure; isotope labelling; molecular dynamics; metal–ion binding; RNA synthesis; Dynamic NMR spectroscopy; Chemical Shift