Researchers look into components of RNA silencing machinery

July 27, 2004

COLLEGE STATION, July 27, 2004 - Up to 95 percent of a person's DNA is believed to be junk DNA. In order to prevent these relics of evolution from rearranging chromosomes and causing disease, natural mechanisms exist to silence them, according to contemporary theories of chromosome biology.

The RNA silencing machinery silences gene expression, by destroying RNA, a molecule that carries out DNA's instructions. Two years ago, components of the RNA silencing machinery were shown to be absolutely required for forming heterochromatin, a chromatin state that silences DNA, suggesting a new rule in biology. But researchers from Texas A&M University and the University of Oregon disagree.

They broke that rule in reporting their findings in the July 25 issue of Science magazine. Funding for the research is supported by grants from the National Institutes of Health.

Knowledge gained from their research will enable scientists to better understand the complexities of chromosome biology, which ultimately will lead to conquering disease by the means of gene therapy, says Rodolfo Aramayo, associate professor of biology at Texas A&M University, who specializes in genetics and studies the biology of meiotic chromosomes. Since the majority of birth defects are caused by chromosomal abnormalities, he says it is absolutely fundamental to understand how chromosomes work.

"Understanding normal chromosome biology is more than a curious scientific endeavor," says Aramayo. "It is a must if we ever are to conquer disease."

In a study with Neurospora crassa, a mold, Aramayo and his colleagues created mutant cells that cannot produce any key components of the RNA silencing mechanism, and discovered that heterochromatin formed just fine.

"Think about a chromosome as being a highway," says Aramayo. "In order to function properly, some sections of the highway must have illumination, which means DNA must be expressed, whereas other sections must not have illumination, which means DNA must not be expressed, or that the region must be heterochromatic.

"Some soldiers carry the duty of turning off certain lights along the highway. Everybody thought these soldiers belong to the RNA silencing machinery, as the rule says. But what our research has shown is that, when we killed these RNA silencing machinery soldiers, someone else is still turning the lights off! We don't know who did it, but we're on our way to find out."

"What we have shown," Aramayo says, "is that cells have evolved more than one way to do the same thing. And this is important, because similar mechanisms might be present in human cells."

In regard to the growing knowledge base in understanding chromosome biology for doing gene therapy, Aramayo says, "Without understanding how chromosomes work, we will never be able to perform gene therapy. Hopefully in the future, we are going to be able to correct genetic mistakes by introducing genes and help people overcome these problems."

Aramayo adds, "Even though we are doing basic research, the implications for society in general are broad."
Other coauthors of the Science magazine article are postdoctoral fellow Dong W. Lee, graduate student Robert J. Pratt of Texas A&M, professor of biology Eric U. Selker, postdoctoral fellows Michael Freitag and Gregory O. Kothe of the University of Oregon.

Texas A&M University

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