A Mg²⁺-responding RNA that controls the expression of a Mg ²⁺ transporter

Mg2⁺ is the most abundant divalent cation in biological systems. It is required for ATP-mediated enzymatic reactions and as a stabilizer of ribosomes and membranes. The enteric bacterium Salmonella enterica serovar Typhimurium harbors three Mg2⁺ transporters and a regulatory system-termed PhoP/PhoQ-whose activity is regulated by the extracytoplasmic levels of Mg²⁺. We have determined that expression of the PhoP-activated Mg²⁺ transporter MgtA is also controlled by its 5′-untranslated region (5′UTR). The 5′UTR of the mgtA gene can adopt different stem-loop structures depending on the Mg²⁺ levels, which determine whether transcription reads through into the mgtA-coding region or stops within the 5′UTR. This makes the mgtA 5′UTR the first example of a cation-responding riboswitch. The initiation of mgtA transcription responds to extracytoplasmic Mg²⁺, and its elongation into the coding region to cytoplasmic Mg²⁺, which provides a singular example where the same ligand is sensed in different cellular compartments to regulate disparate steps in gene transcription. The PhoP-activated Mg²⁺ transporter MgtB is also regulated by Mg²⁺ in a strain lacking the Mg²⁺ sensor PhoQ, suggesting the presence of additional Mg ²⁺-responding devices.