Novel, profound and unexpected roles of long non-coding RNAs (lncRNAs) are 
emerging in critical aspects of gene regulation. Thousands of lncRNAs have been 
recently discovered in a wide range of mammalian systems, related to 
development, epigenetics, cancer, brain function and hereditary disease. The 
structural biology of these lncRNAs presents a brave new RNA world, which may 
contain a diverse zoo of new architectures and mechanisms. While structural 
studies of lncRNAs are in their infancy, we describe existing structural data 
for lncRNAs, as well as crystallographic studies of other RNA machines and their 
implications for lncRNAs. We also discuss the importance of dynamics in RNA 
machine mechanism. Determining commonalities between lncRNA systems will help 
elucidate the evolution and mechanistic role of lncRNAs in disease, creating a 
structural framework necessary to pursue lncRNA-based therapeutics.