Researchers at Washington University School of Medicine in St. Louis have added a gene in the bacterium Salmonella to the short list of genes regulated by a new mechanism known as the riboswitch.
The Salmonella riboswitch is the first to sense and respond to a metal ion, substantially expanding the types of molecules that riboswitches can detect to help cells assess and react to their environment.
First identified in 2002, riboswitches sense when a protein is needed and stop the creation of the protein if it isn't. That in itself isn't remarkable--scientists have been aware for decades of sensors in the cell that can cause molecules to bind to DNA to turn protein production on and off.
A riboswitch, however, doesn't rely on anything binding to DNA; instead, the switch is incorporated into messages for construction of proteins. These messages are protein-building instructions copied from DNA into strands of RNA. The riboswitch is a sensor within the RNA that can twist it into different configurations that block or facilitate the production of the protein encoded in the message.
Previously identified riboswitches respond to organic compounds such as nucleotides and sugars. The Salmonella riboswitch, reported in the April 7 issue of the journal Cell, responds to magnesium ions, key elements in the stability of cell membranes and reactants in an energy-making process that fuels most cells.
"Magnesium ions are essential to the stability of several different critical processes and structures in the cell, so there has to be a fairly intricate set of regulators to maintain consistent levels of it," says senior investigator Eduardo A. Groisman, Ph.D., professor of molecular microbiology. "To approach such a complex system, we study it in a simpler organism, the Salmonella bacterium."
Groisman and his colleagues uncovered the magnesium riboswitch while they were investigating the MgtA gene, which is controlled by the major regulator of Salmonella virulence, the phoP/phoQ system. The MgtA gene codes for a protein that can transport magnesium across the bacterium's cell membrane. Groisman's group showed 10 years ago that the phoP/phoQ system controls when Salmonella makes MgtA.
When Salmonella experiences a low-magnesium environment, phoQ chemically modifies phoP. The changed phoP binds to DNA, increasing the number of times instructions for making MgtA and over 100 other proteins are copied from DNA. But when Salmonella encounters a high-magnesium environment, phoQ deactivates phoP, and fewer copies of the instructions for making MgtA are made.
When Groisman and his colleagues created a mutant strain lacking the phoQ gene, though, they were surprised to find that production of the instructions to make the MgtA protein could still somehow respond to magnesium, producing less of its protein at high magnesium levels.