Mg2+ regulates transcription of mgtA in Salmonella Typhimurium via translation of proline codons during synthesis of the MgtL peptide

Proc Natl Acad Sci U S A. 2016 Dec 27;113(52):15096-15101. doi: 10.1073/pnas.1612268113. Epub 2016 Nov 14.


In Salmonella enterica serovar Typhimurium, Mg2+ limitation induces transcription of the mgtA Mg2+ transport gene, but the mechanism involved is unclear. The 5' leader of the mgtA mRNA contains a 17-codon, proline-rich ORF, mgtL, whose translation regulates the transcription of mgtA [Park S-Y et al. (2010) Cell 142:737-748]. Rapid translation of mgtL promotes formation of a secondary structure in the mgtA mRNA that permits termination of transcription by the Rho protein upstream of mgtA, whereas slow or incomplete translation of mgtL generates a different structure that blocks termination. We identified the following mutations that conferred high-level transcription of mgtA at high [Mg2+]: (i) a base-pair change that introduced an additional proline codon into mgtL, generating three consecutive proline codons; (ii) lesions in rpmA and rpmE, which encode ribosomal proteins L27 and L31, respectively; (iii) deletion of efp, which encodes elongation factor EF-P that assists the translation of proline codons; and (iv) a heat-sensitive mutation in trmD, whose product catalyzes the m1G37 methylation of tRNAPro Furthermore, substitution of three of the four proline codons in mgtL rendered mgtA uninducible. We hypothesize that the proline codons present an impediment to the translation of mgtL, which can be alleviated by high [Mg2+] exerted on component(s) of the translation machinery, such as EF-P, TrmD, or a ribosomal factor. Inadequate [Mg2+] precludes this alleviation, making mgtL translation inefficient and thereby permitting mgtA transcription. These findings are a significant step toward defining the target of Mg2+ in the regulation of mgtA transcription.

Keywords: 50S ribosomal proteins; EF-P translation factor; MgtA Mg2+ transporter; MgtL leader peptide; TrmD methyltransferase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Codon
  • Escherichia coli Proteins / chemistry
  • Gene Deletion
  • Gene Expression Regulation, Bacterial / drug effects
  • Magnesium / chemistry*
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Mutation
  • Peptide Elongation Factors / chemistry
  • Peptides / chemistry*
  • Peptides / genetics
  • Proline / chemistry*
  • Promoter Regions, Genetic / drug effects
  • Protein Biosynthesis
  • RNA, Transfer / chemistry
  • Ribosomes / chemistry
  • Ribosomes / metabolism
  • Salmonella typhimurium / metabolism*
  • Transcription, Genetic / drug effects
  • tRNA Methyltransferases / chemistry


  • Bacterial Proteins
  • Codon
  • Escherichia coli Proteins
  • Membrane Transport Proteins
  • Peptide Elongation Factors
  • Peptides
  • factor EF-P
  • RNA, Transfer
  • Proline
  • TrmD protein, E coli
  • tRNA Methyltransferases
  • Adenosine Triphosphatases
  • MgtA protein, bacteria
  • Magnesium