Na riboswitches regulate genes for diverse physiological processes in bacteria.

Organisms presumably have mechanisms to monitor and physiologically adapt to changes in cellular Na concentrations. Only a single bacterial protein has previously been demonstrated to selectively sense Na and regulate gene expression. Here we report a riboswitch class, previously called the 'DUF1646 motif', whose members selectively sense Na and regulate the expression of genes relevant to sodium biology. Many proteins encoded by Na-riboswitch-regulated genes are annotated as metal ion transporters, whereas others are involved in mitigating osmotic stress or harnessing Na gradients for ATP production. Na riboswitches exhibit dissociation constants in the low mM range, and strongly reject all other alkali and alkaline earth ions. Likewise, only Na triggers riboswitch-mediated transcription and gene expression changes. These findings reveal that some bacteria use Na riboswitches to monitor, adjust and exploit Na concentrations and gradients, and in some instances collaborate with c-di-AMP riboswitches to coordinate gene expression during osmotic stress.