Pushing the boundaries of nucleic acid NMR spectroscopy

Nuclear magnetic resonance (NMR) spectroscopy provides atomic-resolution structural information together with direct insight into nucleic acid dynamics across a wide range of timescales. Recent advances in instrumentation, isotope-labelling strategies, pulse sequence design, sensitivity enhancement and data acquisition have greatly expanded its applicability beyond small DNA and RNA systems. This review highlights how modern NMR enables the characterization of conformational ensembles, transient states and dynamic processes that are difficult to capture by other structural techniques. Particular attention is given to the integration of NMR with complementary structural and computational methods, as well as its growing application to non-canonical nucleic acid structures, large nucleic acid assemblies and studies in native cellular environments. Together, these developments have established NMR as a central tool in structural biology, bridging structure, dynamics and biological function while providing critical insights into the behaviour of nucleic acids and their interactions in health and disease.