’Small RNA’ research cited as breakthrough of the year

A broad group of discoveries about the biological powers of “small-RNA” molecules, some of which were made by researchers at Oregon State University, will be hailed on Friday as the scientific “Breakthrough of the Year” by the journal Science. Science is published by the American Association for the Advancement of Science, the world’s largest general scientific society, and each year the prestigious journal identifies what it believes were the top 10 research advances of the year.

For 2002, the magazine cited a body of work being done by several research groups across the nation on small RNA molecules, calling them “electrifying discoveries, which are prompting biologists to overhaul their vision of the cell and its evolution.” These tiny bits of genetic material were virtually unknown a decade ago but are now on the cutting edge of cell biology, and a better understanding of their function may form the basis for important advances in medicine, agriculture and other fields.

During the year, a major research program at OSU that is being supported by a $1.7 million grant from the National Science Foundation contributed two important publications outlining new findings about these extraordinarily small regulatory molecules, including one article in the journal Science.

“In the fields of molecular and cellular biology, the discoveries about small RNA are now attracting a huge level of interest,” said James Carrington, professor and director of the OSU Center for Gene Research and Biotechnology. “To many people, this may seem very complicated and esoteric, but it’s findings such as this that will soon be opening doors for new advances in medicine, immunology, plant development, and many other areas.

“I know of several companies founded within the past year that are devoted entirely to translating this new research into pharmaceuticals and other products,” Carrington said.

A comprehensive study of DNA, cell biology and genetics evolved steadily from the 1960s through the 1990s, Carrington said. Most of the work focused on conventional, protein coding genes, of which there are thousands. They were easy to study and recognize, and that’s what most molecular biologists spent their careers working on, he said. During that time, most RNA was believed to merely take genetic “orders” from DNA, and through the processes of transcription and translation, help produce the proteins that give cells their function.

In 1993, the first small RNA was discovered, and at the time it was thought to be a biological oddity. It appeared to have some type of regulatory function in the cell but little was known about it.

But research in this field has exploded in just the past year or two. It now includes analysis of micro-RNAs and small interfering RNAs, and other biochemical players, in both plants and animals. A biochemical function of profound importance, once believed to be an odd feature of a single worm species, is now understood to be a major controller of cellular function in practically every species of plant and animal. Including, of course, humans.

After decades of studying cells, Carrington said, a whole new field that scientists never knew existed is wide open for exploration. “As it is with any key scientific advance, the way things work always seem obvious and simple in retrospect,” Carrington said. “Small RNAs offer an elegant, simple and specific mechanism to control gene expression. Looking at it now, it seems obvious that cells would have a mechanism such as this, it makes perfect sense. But until just lately, we never knew where to look. Now we do.”

Scientists have barely scratched the surface of understanding the functions of small RNAs. It’s already clear they play a major role in gene “expression,” or the molecular mechanisms controlling genes that are required for cells to turn into a lung, liver, brain or other cell. It’s also now clear that small RNAs control how whole chromosomes, or regions of chromosomes, are activated or deactivated.

Small RNAs may also hold the key to understanding some types of genetic birth defects, allow new types of disease therapies, understand and control plant development, influence the function of the immune system, help explain some cancers, the function of stem cells, and many other cellular functions.

In the past year, the OSU research program in Carrington’s laboratory has made two important contributions to the understanding of small RNAs. In July, a publication in the journal Plant Cell outlined the first discovery of micro RNAs and small interfering RNAs, which comprise the two major types of small RNAs, in plants. And in September, a publication in the journal Science explained how micro RNA in plants can stop the function of messenger RNA by literally cutting it in half, and thereby exert a strong control over gene expression.

“In our own and other research programs around the country, we’re now learning how micro RNA can shut genes down and prevent their expression,” Carrington said. “So far it appears from our work at OSU that micro RNAs in plants are like hatchets that cut messenger RNAs into nonfunctional pieces. In animals, other researchers have shown that micro RNAs attach to target messenger RNAs and prevent translation into proteins.”

Small-RNAs are now known to be produced by the transcription of tiny genes, in regions of the genome that were previously thought to be vacant or useless DNA. They are extraordinarily tiny and have escaped notice, until recently. However, unlike messenger RNAs, small RNAs are not translated to produce proteins. Their roles are more devoted to control of the process of gene expression or chromosome activity.

“I think one of the most exciting aspects of this work is witnessing the rapid transition of basic research into findings of medical and practical importance,” Carrington said. “The breakthrough of the year recognition suggests that we should expect big things out of small RNAs.”

By David Stauth, 541-737-0787

SOURCE: James Carrington, 541-737-3347