Sep. 23, 2002 CORVALLIS, Ore. – Researchers at Oregon State University have made an important advance in the understanding of "micro-RNA" molecules, which are tiny bits of genetic material that were literally unknown 10 years ago but now represent one of the most exciting new fields of study in biology.
The findings will be reported Friday in the journal Science.
They reveal for the first time a new mechanism by which micro-RNA can stop the function of messenger-RNA by literally cutting it in half, interfering with the normal function of specific messenger RNAs in gene expression.
This "expression" of genes that code for essential proteins is ultimately what controls whether a cell turns into a lung, liver, brain or other cell. Understanding what activates this process – or stops it – is a key to understanding the biological process of life itself, and forms the foundation for advances in medicine, agriculture and other fields.
On this frontier of biology, experts say, the most intriguing new component is micro-RNA, a minuscule type of regulatory molecule that had seemed insignificant even in the extraordinarily tiny, microscopic world of cell biology.
The first micro-RNA, in fact, was only discovered in 1993 and at the time was thought to be a biological oddity in worms. A couple hundred have since been discovered in both plants and animals. But it has only been in just the past few months that scientists working in this area have come to understand the potentially profound importance of micro-RNA.
"For a long time, people really did not know that these micro-RNAs were even there," said James Carrington, professor and director of the OSU Center for Gene Research and Biotechnology. "They were under the radar, and observations of them were limited by our technology. But as we learn more about these regulatory molecules, we're beginning to understand the scope of their biological importance. In molecular biology, micro-RNAs are clearly one of the top two or three discoveries of the past decade."
Every normal cell in complex organisms, such as plants, flies and humans, has a complete copy of the DNA for the entire organism, some 15,000 to 35,000 genes that collectively are thought of as the genetic blueprint for life. But to serve as certain types of cells, such as brain in humans or roots in plants, only a much smaller number of genes within each cell are actually "expressed," or allowed to create the proteins that perform these separate life functions.
"A key focus in biology for a long time has been what controls gene expression," Carrington said.
It is well understood, Carrington said, that two of the key steps between DNA and a functional cell are the processes of transcription and translation. In transcription, single-stranded "messenger RNA" molecules that correspond to each expressed gene are produced. And in translation, the messenger RNA is decoded, resulting in the production of a protein made from some combination of 20 amino acids.
"This is a very complex series of biological processes that requires hundreds of proteins and other factors," Carrington said. "And we're now also learning the role of micro-RNA in controlling expression of some important genes."
Micro-RNAs are actually produced by the transcription of tiny genes, in regions of the genome that were previously thought to be vacant or useless DNA. However, unlike messenger RNAs, micro-RNAs are not translated to produce proteins. Instead, researchers are finding that these micro-RNAs have critical functions in controlling the process of gene expression.
In some recent studies, other scientists found that micro-RNAs can bind to specific messenger RNAs to block the translation or decoding process. In the latest advance made by the OSU researchers, micro-RNAs in the plant Arabidopsis thaliana were found to destroy messenger RNAs instead of blocking its function, by literally cutting it in half.
"Much of our understanding of cell biology is related to this area we call negative regulation, or the processes that stops genes from being expressed," Carrington said. "Anything that improves our knowledge of this process could be quite significant."
For one thing, Carrington said, micro-RNAs might be intimately involved in the normal function of stem cells, those biologically unique cells that, when reproducing, can produce either more stem cells or begin a line of cells that is differentiated into something else, a brain, lung or liver cell.
"It's very important that we learn how cells differentiate and grow normally," Carrington said. "Just about everything in the human body has a genetic component. Genetic abnormalities relate to birth and developmental defects, susceptibility to disease, misregulation of genes. And these same processes are also at work in all other life forms, including plants, and new findings could be applied to crop biotechnology or even traditional plant breeding."
Continued research, Carrington said, will almost undoubtedly find human genetic defects that can be traced to dysfunction of micro-RNAs.
This broad area of research, officials say, has such promise that major new studies are being developed across the nation.
OSU was recently the recipient of a 4-year, $1.7 million grant from the National Science Foundation to study micro-RNAs in Arabidopsis, a plant that works well as a model for genetic research, and the researchers will try to identify the functional messenger RNA targets of different micro-RNAs.
Scientists expect that some of the life processes controlled by micro-RNAs in plants will have been conserved across millions of years of evolution and operate the same way in animals, including humans.
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