The research was first announced at an American Society of Clinical Oncology Meeting, but only now is the full, peer-reviewed report available.
The paper, entitled "Identification of a Novel Gammaretrovirus in Prostate Tumors of Patients Homozygous for R462Q RNASEL Variant," reports that the researchers detected the new virus more frequently in men with mutations in both their copies of RNASEL than in those with at least one normal copy.
Scientists have long speculated about a connection between cancer and infectious diseases. The possible connection has been especially true in the case of prostate cancer because a variant on the viral-defense gene, RNASEL, has been implicated in 15% of prostate cancer cases. The newly discovered virus is closely related to virus associated with leukemia in mice.
"We have made a very fascinating discovery never before seen in humans that is very similar to one found in a mammal that causes cancer," said Dr. Eric Klein of the Cleveland Clinic. "But we have not proven this virus causes prostate cancer."
pathogens.plosjournals
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.
medschool.wustl/