A Mg²⁺-responding RNA That Controls the Expression of a Mg²⁺ Transporter

Abstract

Mg²⁺ is the most abundant divalent cation in biological systems. It is required for ATP-mediated enzymatic reactions and asa stabilizer of ribosomes and membranes. The enteric bacterium Salmonella enterica serovar Typhimurium harbors threeMg²⁺ transporters and a regulatory system—termed PhoP/PhoQ—whose activity is regulated by the extracytoplasmiclevels of Mg²⁺. We have determined that expression of the PhoP-activated Mg²⁺ transporter MgtA is also controlled by its5'-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. Thismakes the mgtA 5'UTR the first example of a cation-responding riboswitch. The initiation of mgtA transcription responds toextracytoplasmic Mg²⁺, and its elongation into the coding region to cytoplasmic Mg²⁺, which provides a singular examplewhere the same ligand is sensed in different cellular compartments to regulate disparate steps in gene transcription. ThePhoP-activated Mg²⁺ transporter mgtB is also regulated by Mg²⁺ in a strain lacking the Mg²⁺ sensor PhoQ, suggesting thepresence of additional Mg²⁺-responding devices.