A Mg 2 +-responding RNA That Controls the Expression of a Mg 2 + Transporter

is an essential cofactor for all ATP-mediated enzymatic reactions and because Mg helps maintain the stability of membranes as well as of certain macromolecular complexes such as the ribosome (Reinhart 1988). Therefore, cells must preserve physiological Mg concentrations, which might not be the same in different subcellular compartments. To achieve this task, cells need to have the means to sense the levels of Mg as well as the ability to modify the movement of this essential cation across biological membranes and/or from storage locations. The gram-negative bacterium S. enterica serovar Typhimurium harbors a Mg-responding regulatory system (i.e., PhoP/PhoQ) (Groisman 2001), three Mg transporters (i.e., CorA, MgtA, and MgtB) (for review, see Smith and Maguire 1998; Maguire 2006), and an integral membrane protein that is required for optimal growth in low Mg (i.e., MgtC). The PhoP/PhoQ system consists of the PhoQ protein, a sensor for extracytoplasmic Mg, and the transcriptional regulator PhoP (Groisman 2001). When Salmonella experiences low Mg, the PhoQ protein promotes phosphorylation of the PhoP protein, which can then bind to its target promoters to modify gene transcription: PhoP-activated genes are turned on and PhoP-repressed genes are turned off. And when Salmonella faces high Mg, PhoQ promotes the unphosphorylated state of the PhoP protein, which is unable to bind to its target promoters and results in no transcription of PhoP-activated genes and derepression of PhoPrepressed genes (Soncini et al. 1996; Castelli et al. 2000; Chamnongpol and Groisman 2000; Montagne et al. 2001; Chamnongpol et al. 2003). The CorA protein can mediate both influx and efflux of Mg and does not exhibit sequence similarity to the MgtA or MgtB proteins, which are 50% identical to one another and solely mediate Mg influx (for review, see Smith and Maguire 1998; Maguire 2006). MgtA and MgtB also differ from CorA in that transcription of the mgtA and mgtB genes is directly regulated by the PhoP protein in response to extracytoplasmic Mg sensed by the PhoQ protein (Soncini et al. 1996; Yamamoto et al. 2002; Zwir et al. 2005), whereas expression of CorA responds neither to Mg nor to the PhoP/PhoQ system (Chamnongpol and Groisman 2002). Yet, the activity of the CorA transporter is enhanced in a phoP mutant by an unknown mechanism (Chamnongpol and Groisman 2002). The PhoP/PhoQ system controls expression of about 3% of the genome. This includes not only the genes encoding the Mg transporters MgtA and MgtB, but also the genes coding for products that modify the negatively charged residues in the lipopolysaccharide (i.e., LPS), which are neutralized primarily by Mg (Groisman et al. 1997; Groisman 2001). The LPS is the dominant molecule in the outer leaflet of the outer membrane of Escherichia coli and Salmonella, and it has been estimated that more than one-third of the total Mg content is located in the LPS (Groisman et al. 1997). The PhoP/PhoQ system and the MgtA and CorA transporters are widely distributed within the family Enterobacteriaceae (Smith and Maguire 1995; Blanc-Potard and Groisman 1997). This is in contrast to the sporadic distribution of the MgtB and MgtC proteins. This paper discusses the discovery, characterization, and function of the first example of an Mgresponding riboswitch, and how such RNA regulates cytoplasmic Mg levels. A Mg-responding RNA That Controls the Expression of a Mg Transporter