Researchers here have discovered a new mechanism used by cells - and manipulated by retroviruses - to control the making of certain essential proteins, including some involved in cancer.
The mechanism uses an enzyme called RNA helicase A (RHA), which is made by the cell.
The study by researchers with The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute and the OSU College of Veterinary Medicine appears online in the journal Nature Structural and Molecular Biology.
"Our findings provide important insights into how cells regulate certain growth-proteins, many of which play an important role in cancer, and how viruses use cell mechanisms to establish an infection," says principal investigator Kathleen Boris-Lawrie, professor of veterinary biosciences and a researcher with the OSU Comprehensive Cancer Center .
The study shows, for example, that when RHA is knocked out, the spleen necrosis virus, a retrovirus Boris-Lawrie and her collaborators were studying as a vector for gene therapy, was unable to make certain proteins. Thus, RHA might be a cellular target for future antiretroviral drugs. (Current antiretroviral drugs target the virus itself, which often becomes resistant to them, rendering the drugs ineffective. Antiretroviral drugs that affect cellular targets might be less prone to resistance.)
"Retroviruses seem to take advantage of RHA to enhance production of their own proteins, and cells use it to control the amount of particular proteins they make, many of which are involved in growth control," says Boris-Lawrie.
"The cell has to keep tight control of these proteins to be sure they are not made at the wrong time."
Cells use a four-step process to make most proteins. First, the cell makes a copy of a gene. The copy is called messenger RNA, or mRNA, and it describes the structure of the needed protein. Next, the mRNA is processed to remove non-essential information. Then, the message travels from the cell nucleus to another location, the cell cytoplasm. Last, other cell machinery translates the message and assembles the protein.
The findings by Boris-Lawrie and her collaborators show that RHA can play an important role in determining whether the last step of this process - translating the message and making the protein - actually happens.
For this study, the researchers first used mass spectroscopy to identify the cell protein and learned that the protein was RHA.
Then the researchers knocked out the RHA protein and learned that the retrovirus stopped making several vital proteins.