Magnesium regulates transcription of the mgtA (magnesium transporter) gene in Salmonella enterica serovar typhimurium via prolyl-bond formation during translation of the mgtL leader ORF

In Enterobacteriaceae, the mgtA gene encodes a P-type ATPase that mediates Mg2+ uptake and is up-regulated by the PhoQP two-component system during invasion of host epithelial cells and macrophages. The regulation of mgtA has recently gained special interest given that it exists at several stages, including transcription, post-transcription and post-translation, in response to Mg2+ availability. The mgtA mRNA has a 264-nucleotide 5’ leader that contains a 17 codon, proline-rich ORF, termed mgtL, whose translation has been proposed to affect the folding of the 5’ leader mRNA, which in turn regulates whether transcription is terminated before the mgtA structural gene at high Mg2+ concentrations, or is allowed to read through at limiting Mg2+ concentrations. We hypothesize that Mg2+ directly regulates translation of mgtL by facilitating prolyl-bond formation. We find that rescue of ribosome stalling at proline codons of mgtL by translation factor EF-P and methylation of tRNAPro with m1G37 by TrmD both play roles in the regulation of mgtL translation. Of potential significance is that TrmD is dependent on Mg2+ for its tRNA methylation activity, implying an underlying role of Mg 2+ in the regulation. We suggest a complex interaction between Mg 2+, proline, EF-P and TrmD in the regulation of mgtL translation and mgtA transcription. In addition, we provide preliminary results implicating an unknown transcription factor and other potential growth conditions in the regulation of mgtA expression