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.