Guanidine-sensing riboswitches: How do they work and what do they regulate?

After remaining an orphan for over a decade, the ykkC riboswitch family (ykkC, mini-ykkC, and ykkC-III) was recently characterized as guanidine-specific genetic regulatory elements (guanidine-I, II, and III). They respond to increased levels of intracellular guanidine by turning on genes involved in guanidine export and breakdown. Their existence suggests that regulation of intracellular guanidine levels could be an important piece of bacterial physiology which was not appreciated previously. Structural biologists moved exceptionally fast to reveal the guanidine-sensing mechanisms of these riboswitches at the atomic level. The crystal structures of all three guanidine family members have been determined. They appear to represent three independently evolved RNA sensors, with distinct tertiary folds but surprisingly similar guanidine-binding cores. A few key questions remain to be addressed: It is not known which metabolic pathway(s) may lead to guanidine accumulation and the function of close relatives to the guanidine-I riboswitch that do not respond to guanidine remains unclear. The continued characterization of these and other orphan cis-regulatory elements represents an orthogonal approach to reveal new facets of bacterial physiology. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Riboswitches RNA Structure and Dynamics > RNA Structure, Dynamics, and Chemistry.