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.
Researchers used a computer program to determine how RNA copied from the MgtA gene might be folding up. The program predicted RNA copied from the gene could have two significantly different configurations. Because of the significant differences between these configurations, Groisman, who is also a Howard Hughes Medical Institute investigator, became interested in a region at the beginning of the RNA strand that contains no protein-building instructions. He theorized that it might be a riboswitch that responded to high magnesium levels by twisting the RNA into a configuration where its protein-building instructions somehow could not be used or were invalidated.
"One of our tests to see if this was something more than a computer fantasy was to take this segment that contains no protein-building instructions off the MgtA gene and paste it into another genetic configuration," Groisman says. "We wanted to see if it conferred sensitivity to magnesium levels, which it did."
In addition, Groisman’s group showed that one RNA configuration was common in low magnesium levels while another was common in high magnesium levels.
They also searched the genomes of other bacteria with MgtA genes to see if their DNA included a sequence similar to the riboswitch in Salmonella. In six other bacteria, a similar sequence precedes the MgtA gene and can twist RNA copied from it into different configurations.
"Normally you would expect to find that a DNA sequence that is conserved among different species is encoding part of a protein," Groisman says. "But here we’re talking about a part of a message that does not encode a protein. So why would it be conserved? There must be some important role that the sequence is fulfilling that is leading to its conservation, such as giving the cell expanded ability to sense and respond to magnesium levels."
Follow-up inquiries are already underway to locate the riboswitch’s "brain"--the section of the RNA strand that responds to magnesium; and to learn how the high-magnesium configuration of the RNA disrupts final production of the protein.
Michael Purdy | EurekAlert!
Designer cells: artificial enzyme can activate a gene switch
22.05.2018 | Universität Basel
Flow of cerebrospinal fluid regulates neural stem cell division
22.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.
The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...
Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.
Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
22.05.2018 | Life Sciences
22.05.2018 | Life Sciences
22.05.2018 | Life Sciences