RNAs have emerged as a major target for diagnostics and therapeutics approaches. Regulatory nonprotein-coding RNAs (ncRNAs) in particular display remarkable ver- satility. They can fold into complex structures and interact with proteins, DNA, and other RNAs, thus modulating activity, localization, or interactome of multi-protein complexes. Thus, ncRNAs confer regulatory plasticity and represent a new layer of reg- ulatory control. Interestingly, long noncoding RNAs (lncRNAs) tend to acquire complex secondary and tertiary structures and their function—in many cases—is dependent on structural conservation rather than primary sequence conservation. Whereas for many proteins, structure and its associated function are closely con- nected, for lncRNAs, the structural domains that determine functionality and its inter- actome are still not well understood. Numerous approaches for analyzing the struc- tural configuration of lncRNAs have been developed recently. Here, will provide an overview of major experimental approaches used in the field, and discuss the poten- tial benefit of using combinatorial strategies to analyze lncRNA modes of action based on structural information.DOI: 10.1002/bies.202000027 - 2020

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