Media Contacts: Dr. Steven A. Lommel, 919/515-6990 or [email protected]

Dr. Tim L. Sit, 919/515-6991 or [email protected]

Tim Lucas, News Services, 919/515-3470 or [email protected]

Aug. 5, 1998

New Study Finds RNA Can Control Gene Expression

EMBARGOED FOR RELEASE AT 5 P.M. THURSDAY, AUG. 6

A study by North Carolina State University researchers shows, for the first time, that RNA can control gene expression.

The study, published in the Aug. 7 issue of the journal Science, finds that the interaction of two RNA components is responsible for making protein in the red clover necrotic mosaic virus. Though the virus itself isn't an important plant disease, the discovery may have profound implications in agricultural research and evolutionary biology.

"Previously, we knew that RNA had a number of functions, but gene expression was not one of them. This is the first time we've been able to show that an RNA-to-RNA interaction can turn on a gene," says Dr. Steven A. Lommel, professor of plant pathology at NC State.

"Every year, scientists are finding that RNA can perform more cellular functions that, like gene expression, were once attributed solely to proteins," says Lommel. "Our finding is one more piece of evidence to support the hypothesis that RNA was the first molecule of life."

Agricultural researchers may be able to use the new knowledge to genetically engineer better crops, he says. "We may be able to use this RNA function -- two RNAs binding to express a gene -- as a molecular tool to regulate a foreign gene that has been introduced into a plant. Or we could use it as a regulatory element to temporarily control the expression of a gene." The discovery also might have an impact on the study of human viruses such as rubella and hepatitis C, which, like the red clover necrotic mosaic virus, have subgenomic RNA, he says.

Until the NC State team made its discovery, scientists thought gene expression was a function controlled only by proteins. "Usually, a number of proteins bind to a promoter region to turn the gene on or off," says Dr. Tim L. Sit, an NC State research associate in plant pathology and one of Lommel's co-authors.

In the case of the red clover necrotic mosaic virus, however, Lommel and his team found a different mechanism at work. The virus contains two RNA components; a polycistronic RNA-1, rna--2

which encodes the viral polymerase (the RNA-reading protein) and capsid protein that forms the virus' protective shell; and RNA-2, which encodes the viral movement protein required for the cell-to-cell spread of infection, Sit explains. "We found that for the RNA-1 component to express the capsid protein, it had to bind with the other RNA molecule," he says.

Next up, Lommel says, is to see if RNA-to-RNA promoter mechanisms are at work in other organisms. "It may be a widely distributed function of RNA that until now scientists have not documented, or it may occur only in viruses, or only in this virus," he says.

The red clover necrotic mosaic virus is an obscure plant pathogen but is a good model virus for study, Lommel says, because of its relatively simple genetic makeup -- its genome is composed of only two single-stranded RNA components.

NC State has applied for a patent on the discovery.

Recent NC State graduate student Andrew A. Vaewhongs was a member of Lommel's team, and co-authored the Science paper. The team's research was funded by the National Science Foundation.

-- lucas --

NOTE TO EDITORS: An abstract of the NC State researchers' Science paper follows. For copies of the full article, call or e-mail Tim Lucas or Sara Frisch, NC State News Services, at (919) 515-3470 or [email protected] and [email protected].

"RNA-Mediated Trans-Activation of Transcription From a Viral RNA" Published Aug. 7, 1998 in Science, Vol. 281 Authors: Tim L. Sit, Andrew A. Vaewhongs, Steven A. Lommel, Department of Plant Pathology, North Carolina State University

ABSTRACT: The red clover necrotic mosaic virus genome is composed of two single-stranded RNA components, RNA-1 and RNA-2. The viral capsid protein is translated from a subgenomic RNA (sgRNA) that is transcribed from genomic RNA-1. Here, a 34-nucleotide sequence in RNA-2 is shown to be required for transcription of sgRNA. Mutations that prevent base-pairing between the RNA-1 subgenomic promoter and the 34-nucleotide trans-activator prevent expression of a reporter gene. A model is proposed in which direct binding of RNA-2 to RNA-1 trans-activates sgRNA synthesis. This RNA-mediated regulation of transcription is unusual among RNA viruses, which typically rely on protein regulators.

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