AMHERST — Molecular biologists at the University of Massachusetts Amherst have for the first time shown how a micro RNA molecule directs the potentially disease-killing function of the body’s lymphocytes.

Molecular biologists, led by Leonid Pobezinsky and his wife and research collaborator Elena Pobezinskaya, published results that show how the Lethal-7 (let-7) molecule serves as a control hub to direct the function of cytotoxic T lymphocytes, and thus regulate their cell-killing activities.

Further, the researchers found that when let-7 levels are low or absent, the body’s T cells can potentially turn into disease “super killers,” Pobezinsky says. The discovery is a significant advance in the quest to enlist the body’s own immune defenses, a technique known as adaptive immunotherapy. It may more effectively attack disease-causing agents such as invasive cancer and chronic infections like HIV, he adds. Details appear now in the open-access journal ELife.

As Pobezinsky explains, “We get cancer because CD8 T-cells are not always efficient and cancer can overcome them. Our lab looks at the molecular mechanisms that regulate the cytotoxic efficiency of T cells.” He and colleagues report finding the control mechanism in a tiny strand of micro RNA, only 20-30 nucleotides long, that determines how effective T cells will be in attacking disease.

“This was very interesting because when microRNAs were discovered over 20 years ago, people thought it was a product of RNA degradation. They were considered to be used fragments, like dust. They are so tiny, nobody paid attention to them,” he notes. “But since then, people have gradually been discovering what they really do. Our work is continuing that.”

The research group led by the Pobezinskys includes his Ph.D. student and first author Alexandria Wells, UMass Amherst molecular biologist Michele Markstein, who provided the computational analysis to identify let-7 targets and how let-7 regulates the genome, and UMass Medical School immunologist Raymond Welsh, a specialist in cytotoxic CD8 T cells.

“We’d like to develop a way to suppress or enhance immune response,” Pobezinsky says. “We might be able to combine this with adaptive immunotherapy to enhance immune function, so we would use a person’s own T cells, treat them in vitro, then to put back super killer T cells to boost their immune response. It’s very promising, I feel it’s a real possibility to go from this fundamental research and have an immediate application. For us it is very, very satisfying to do something for society.”