In a Human Virus, New Method to ID MicroRNA Targets Proves Its Value

MicroRNAs are a very important, newly recognized type of molecule naturally encoded within the human genome. MicroRNAs, or miRNAs, help determine which gene products are produced in a cell. Some miRNAs have been found to act abnormally in cancers, and a few years ago miRNAs were found in disease-causing viruses.

Scientists have much to learn about miRNAs, but few doubt the role of miRNAs in human health and disease. The discoverers of miRNAs are the most recent recipients of what is arguably the most prestigious US recognition for basic biomedical research, the Albert Lasker Basic Medical Research Award.

But it remains a challenge to figure out which genes are the targets of specific miRNAs. A research team led by UCSF virologist Don Ganem, MD, has recently reported a powerful, new approach in the scientific journal Nature Genetics.

Ganem, a Howard Hughes Medical Institute investigator at UCSF, demonstrated the new approach by using the Kaposi’s sarcoma-associated herpesvirus, the causative virus of an AIDS-associated cancer that was first cultured by Ganem more than a decade ago.

Ganem’s lab team used a series of rigorous lab protocols to narrow down suspected human gene targets of key viral miRNAs. MicroRNAs inhibit genes from making protein, in part by interfering with the ability of other kinds of RNA, called messenger RNA (mRNA), to make proteins. Ganem’s new approach differs from other methods in that it focuses on changes in the levels of these mRNAs — rather than on the proteins they encode — when they are targeted by miRNAs.

Ganem’s broader ambition is to use these new methods to discover general principles of miRNA action. He wants to use these principles to better predict and more quickly identify the targets of specific miRNAs, and to figure out the biochemical mechanisms through which miRNAs help control gene activity. The method his team developed is generally applicable to other miRNAs, including those produced by the human genome. Therefore, other researchers may use Ganem’s methods to further their own fundamental investigations into this frontier of biology and genetics.

The work of Ganem’s lab team, in addition to developing a new method, also sheds new light on control of the virus’s life cycle — a balance between quiet latency within cells and active viral proliferation and cellular destruction. “The more we learn about how viruses carry out their mission, the better we will be able to come up with new strategies for fighting them,” Ganem says.

Related Links:

Ganem Lab at UCSF
UCSF Department of Microbiology and Immunology

Michael T. McManus, PhD
UCSF Diabetes Center

Albert Lasker Basic Medical Research Award 2008 Winners
Lasker Foundation