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!
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
29.03.2017 | Materials Sciences
29.03.2017 | Physics and Astronomy
29.03.2017 | Earth Sciences