NEW DISCOVERY ABOUT GENES HAS IMPLICATIONS FOR GENETIC THERAPY

COLUMBUS, Ohio -- Researchers here have discovered that introns -- parts of genes long thought to play no role in conveying genetic information -- may well be the key to determining where new information is transferred into a gene.

If true, the finding has important implications for potential future use in guiding genetic therapy. Current techniques can insert new information into genes but exactly where that information is transferred is often left to chance.

The new intron approach could allow researchers to insert new information at specific sites along a gene, allowing considerably more control than is now possible. Ohio State University researchers reported their findings in the May 23 issue of the British science journal Nature.

They also believe the discovery provides a window into how some of the earliest organisms evolved several billions of years ago since the introns function as very primitive genetic elements.

Alan Lambowitz, Ohio Eminent Scholar in Molecular Genetics, along with doctoral student Jian Yang and postdoctoral researcher Steven Zimmerly, focused on the simple organism Saccharomyces cerevisiae, ordinary baker's yeast. The yeast is widely used both in brewing and by geneticists for their research.

Genes are basically long strands of DNA that carry the essential genetic information needed to produce a protein. Scientists believed that only certain DNA sequences -- called exons -- carried useful information. Other pieces of "junk DNA" called introns are interspersed as "spacers" between the exons along the gene.

Lambowitz' team found that certain introns could move from place to place along a gene, inserting themselves at specific points along the DNA strand, and transferring genetic information in the process.

"This is really a very, very interesting finding," he said. "Previously, no one believed that it was possible."

This ability of the introns to pick and choose a site along the gene where they would insert themselves convinced the researchers that they were seeing a holdover to a similar mechanism that must have taken place in the earliest evolutionary stages of primitive one-celled animals-- at least a billion years ago.

"We were interested in the basic question of how these introns insert themselves into different genes," Lambowitz explained. "We wanted to know where introns came from and how they move.

"This class of introns appears very primitive, as if they were the ancestors of introns found in higher organisms."

Lambowitz believes that the introns are "parasites" on the genome, and behave similar to the way retroviruses inhabit an organism. He suggested that retroviruses might even have evolved originally from these kinds of introns.

"Their (the introns') only function is to replicate themselves, but in that process, they fundamentally influence the nature of the gene structure," he said. Such changes can drastically change the function of a gene.

"These introns can move around from place to place on the gene and spread themselves by inserting into different genes. They do this naturally," Lambowitz said. "We were interested in the mechanism by which they do this." He said that the mechanism involves integration of the intron's RNA into the double-stranded DNA of the gene. The information in the RNA is eventually transferred into the DNA through this process.

"This is a really surprising find. No one suspected that they could use this mechanism."

In a few experiments so far, the researchers have been able to modify some of the information carried by the introns and transfer it to the genes at a very specific site. Much more work will be required before the process could be used for any therapeutic purposes, he said.

Lambowitz's team, along with researcher Phillip S. Perlman, a biochemist from the Southwestern Medical Center in Dallas, was supported by grants from the National Institute of General Medical Science. The researchers have applied for a patent to protect their process.

Contact: Alan Lambowitz, (614) 292-5606; Lambowitz.1@osu.edu

Written by Earle Holland; Holland.8@osu.edu


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