So Breaker and his colleagues put the RNA in a test tube and began to mix in different chemicals, observing whether or not they bound to the riboswitch. They worked through a long list of more common chemicals before they stumbled on fluoride. The addition of fluoride was an accident -- fluoride was a contaminant in a sample of a different chemical they were testing.
Once Breaker's group found that the riboswitch bound to fluoride, they were able to show that the genes controlled by the riboswitch are those that help the cell fight the toxicity of fluoride. Fluoride, a negatively charged ion, binds aggressively to some metabolites and essential enzymes. If fluoride floods a cell, it can quickly shut down cellular processes. The fluoride-sensing riboswitch, Breaker's team discovered, turns on a gene coding for ion channels that transport fluoride back out of the cell.
"This riboswitch is detecting fluoride buildup in the cell and turning on genes to help overcome that buildup," says Breaker. Whether or not the riboswitch is successful, and fast enough, determines whether a bacterium can fight the effects of fluoride.
"Our data not only help explain how cells fight the toxicity of fluoride, but it also gives us a sense of how we might be able to enhance the antimicrobial properties of fluoride," says Breaker. "In the future we might be able to use this knowledge to make fluoride even more toxic to bacteria."
Blocking the fluoride channel, for example, makes cells 200 times more sensitive to fluoride, the researchers showed. Finding other ways to enhance fluoride's effectsby inactivating the riboswitch or shutting off other downstream g
|Contact: Jim Keeley|
Howard Hughes Medical Institute