Thousands of long non-coding RNAs have been discovered in recent years, leading some to claim there may be as many functional RNAs as proteins. The hoopla, however, has left some wondering whether the field is all bark and no bite.
Many recent functional studies have demonstrated clear visible phenotypes for long non-coding RNAs, quieting some skeptics trying to wrap their heads around these enigmatic molecules. In the wake of these findings, a second controversy has raged – do these long RNAs have structures and are they important for function?
A large number of structural investigations have shown lncRNAs across the genome have clear indications of secondary structure. Detailed studies of HOTAIR and XIST show these to have highly intricate multi-domain structures.
Taking the next step, Hawkes et al. (2016) recently performed one of the first structure-function studies of a lncRNA, looking at the plant system COOLAIR, which is important for the timing of flowering (FLC gene regulation). They show the RNA to have a complicated multiple helix junction and two long helices connected by an unusual extended loop. The architecture of this RNA shows remarkable conservation, surviving evolutionary selection over ten million years. Interestingly, the length of one of the helices is linked to trait variation, potentially allowing for adaptation to a changing environment.
In a related study, Xue et al. (2016) see a similar extended loop motif, this time in the Braveheart lncRNA. They present a clear structure-function relationship, proving this structural element to be critical for cardiomyocyte commitment and binding to a zinc finger protein.