Abstract
All cells must manage deficiency, sufficiency, and excess of essential metal ions. Although iron has been one of most important metals in biology for billions of years, the mechanisms by which bacteria cope with high intracellular iron concentrations are only recently coming into focus. Recent work has suggested that an RNA riboswitch (czcD or "NiCo"), originally thought to respond specifically to Co(II) and Ni(II) excess, is more likely a selective regulator of Fe(II) levels in important human gut bacteria and pathogens. We discuss the challenges and controversies encountered in the characterization of iron-responsive riboswitches, and we suggest a physiological role in responding to iron overload, perhaps during anaerobiosis. Finally, we place these riboswitches in the context of the better understood mechanisms of protein-based metal ion regulation, proposing that riboswitch-mediated mechanisms may be particularly important in regulating transport of the weakest-binding biological divalent metal ions, Mg(II), Mn(II), and Fe(II).