Divalent ions fulfill essential cellular roles and are required for virulence by certain bacteria. Free intracellular Mg2+ can approach 5 mM, but at this level, Mn2+, Ni2+, or Co2+ can be growth-inhibitory, and Mg2+-fluoride is toxic. To maintain ion homeostasis, many bacteria have evolved ion sensors embedded in the 5′-leader sequences of mRNAs encoding ion uptake or efflux channels. Here, we review current insights into these "metalloriboswitches," emphasizing ion-specific binding by structured RNA aptamers and associated conformational changes in downstream signal sequences. This riboswitch-effector interplay produces a layer of gene regulatory feedback that has elicited interest as an antibacterial target.
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