Discovering riboswitches: the past and the future

Riboswitches are structured noncoding RNA domains used by many bacteria to monitor the concentrations of their target ligands and regulate gene expression accordingly. In the past 20 years, over 55 distinct classes of natural riboswitches have been discovered that selectively sense small molecules or elemental ions, and thousands more are predicted to exist. Evidence suggests that some riboswitches might be direct descendants from the RNA-based sensors and switches that were likely present in ancient organisms before the evolutionary emergence of proteins. Herein, we provide an overview of the current state of riboswitch research, focusing primarily on the discovery of riboswitches, and speculate on the major challenges facing researchers in the field.