Marnie
Frequent Contributor (5K+ posts)
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Read the last sentence in the following:
Salmonella bacteria use RNA to assess and adjust magnesium levels
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.
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.
Borrelia burgdorferi EbfC, a Novel, Chromosomally Encoded Protein, Binds Specific DNA Sequences Adjacent to erp Loci on the Spirochete's Resident cp32 Prophages.
Babb K, Bykowski T, Riley SP, Miller MC, Demoll E, Stevenson B.
Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, MS421 W. R. Willard Medical Education Building, Lexington, KY 40536-0298. [email protected].
All examined isolates of the Lyme disease spirochete, Borrelia burgdorferi, naturally maintain numerous variants of a prophage family as circular cp32 episomes. Each cp32 carries a locus encoding one or two different Erp outer membrane, surface-exposed lipoproteins. Many of the Erp proteins bind a host complement regulator, factor H, which is hypothesized to protect the spirochete from complement-mediated killing.
We now describe the isolation and characterization of a novel, chromosomally encoded protein, EbfC, that binds specific DNA sequences located immediately 5' of all erp loci.
***This is one of the first site-specific DNA-binding proteins to be identified in any spirochete.***
The location of the ebfC gene on the B. burgdorferi chromosome suggests that the cp32 prophages have evolved to use this bacterial host protein for their own benefit and that EbfC probably plays additional roles in the bacterium.
A wide range of other bacteria encode homologs of EbfC, none of which have been well characterized, so demonstration that
B. burgdorferi EbfC is a site-specific DNA-binding protein has broad implications across the eubacterial kingdom.
PMID: 16740939
Is Bb doing the same, but in a different "location"?
As I understand it, RNA is UNstable compared to DNA. RNA contains one more OH molecule.
It was recently discovered, it is not DNA that causes gene expression, but is RNA! Now...to give our "offspring" a genetic code, the genes have to be stabilized. But backing up a notch...RNA is the contributing factor. (RNA->DNA).
Carol in PA
Frequent Contributor (5K+ posts)
Member # 5338
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Marnie, What do you see as the application to Lyme?
Carol
Posts: 6947 | From Lancaster, PA | Registered: Feb 2004
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Marnie
Frequent Contributor (5K+ posts)
Member # 773
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I think Bb, like salmonella, CAUSES (multiple reasons) Mg to drop. I think it might be locking onto our DNA making this happen.
Bb needs high Ca levels. It does NOT want high Mg levels (maintained).
It needs Ca to help it to make its lipids. I posted this today under Cave's spirochete info., but will post also separately.
Posts: 9424 | From Sunshine State | Registered: Mar 2001
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