The Biochemical Landscape of Riboswitch Ligands

Over 55 distinct classes of riboswitches that respond to small metabolites or elemental ions have been experimentally validated to date. The ligands sensed by these riboswitches are biased in favor of fundamental compounds or ions that are likely to have been relevant to ancient forms of life, including those that might have populated the “RNA World”, which is a proposed biochemical era that predates the evolutionary emergence of DNA and proteins. In the following text, I discuss the various types of ligands sensed by some of the most common riboswitches present in modern bacterial cells and consider implications for ancient biological processes based on the proven capabilities of these RNA-based sensors. Although most major biochemical aspects of metabolism are represented by known riboswitch classes, there are striking sensory gaps in some key areas. These gaps could reveal weaknesses in the performance capabilities of RNA that could have hampered RNA World evolution, or these could highlight opportunities to discover additional riboswitch classes that sense essential metabolites.