Transcriptional regulation of magnesium transporters contributes to cellular homeostasis in bacteria

Magnesium (Mg2+) is an essential element in biology due to its abundance and unique chemical properties. However, the dynamics of Mg2+ homeostasis and the role of this process in cellular physiology are not well understood. I have characterized two mechanisms in the bacterium Salmonella enterica serovar Typhimurium that regulate expression of Mg2+ transporters. First, structural elements in the mRNA leader of the Mg2+ channel gene corA couple accessibility of a binding site for the transcription termination factor Rho to translation of a short open reading frame, leading to an inverse relationship between corA transcription and translational efficiency. Similar mechanisms regulate all three Mg2+ transporters in Salmonella, indicating that increased Mg2+ uptake may be beneficial during translational impairment. Second, the small molecule alarmone (p)ppGpp represses transcription of all Mg2+ transporter genes in Salmonella to prevent deleterious Mg2+ accumulation during programmed translational arrest. Because Rho and (p)ppGpp both balance transcription and translation—two highly Mg2+-dependent processes—on a cell-wide basis, I propose that Rho- and (p)ppGpp-mediated regulation of Mg2+ uptake stabilizes gene expression at large and thus broadly contributes to cellular homeostasis