A Translation-Aborting Small Open Reading Frame in the Intergenic Region Promotes Translation of a Mg(2+) Transporter in Salmonella Typhimurium

Bacterial mRNAs often harbor upstream open reading frames (uORFs) in the 5′ untranslated regions (UTRs). Translation of the uORF usually affects downstream gene expression at the levels of transcription and/or translation initiation. Unlike other uORFs mostly located in the 5′ UTR, we discovered an 8-amino-acid ORF, designated mgtQ, in the intergenic region between the mgtC virulence gene and the mgtB Mg(2+) transporter gene in the Salmonella mgtCBRU operon. Translation of mgtQ promotes downstream mgtB Mg(2+) transporter expression at the level of translation by releasing the ribosome-binding sequence of the mgtB gene that is sequestered in a translation-inhibitory stem-loop structure. Interestingly, mgtQ Asp2 and Glu5 codons that induce ribosome destabilization are required for mgtQ-mediated mgtB translation. Moreover, the mgtQ Asp and Glu codons-mediated mgtB translation is counteracted by the ribosomal subunit L31 that stabilizes ribosome. Substitution of the Asp2 and Glu5 codons in mgtQ decreases MgtB Mg(2+) transporter production and thus attenuates Salmonella virulence in mice, likely by limiting Mg(2+) acquisition during infection.