Getting to the bottom of lncRNA mechanism: structure–function relationships

While long non-coding RNAs are known to play key roles in disease and development, relatively few structural studies have been performed for this important class of RNAs. Here, we review functional studies of long non-coding RNAs and expose the need for high-resolution 3-D structural studies, discussing the roles of long non-coding RNAs in the cell and how structure–function relationships might be used to elucidate further understanding. We then describe structural studies of other classes of RNAs using chemical probing, nuclear magnetic resonance, small-angle X-ray scattering, X-ray crystallography, and cryogenic electron microscopy (cryo-EM). Next, we review early structural studies of long non-coding RNAs to date and describe the way forward for the structural biology of long non-coding RNAs in terms of cryo-EM.