Long Non-coding RNA Structure and Function: Is There a Link?

RNA has emerged as the prime target for diagnostics, therapeutics and the development of personalized medicine. In particular, the non-coding RNAs (ncRNAs) that do not encode proteins, display remarkable biochemical versatility. They can fold into complex structures and interact with proteins, DNA and other RNAs, modulating the activity, DNA targets or partners of multiprotein complexes. Thus, ncRNAs confer regulatory plasticity and represent a new layer of epigenetic control that is dysregulated in disease. Intriguingly, for long non-coding RNAs (lncRNAs, >200 nucleotides length) structural conservation rather than nucleotide sequence conservation seems to be crucial for maintaining their function. LncRNAs tend to acquire complex secondary and tertiary structures and their functions only impose very subtle sequence constraints. In the present review we will discuss the biochemical assays that can be employed to determine the lncRNA structural configurations. The implications and challenges of linking function and lncRNA structure to design novel RNA therapeutic approaches will also be analyzed.