( o cut out malfunctioning genes. Intr...)Molecular machine may lead to new drugs to combat human diseases

Introns' unique capability of cutting and pasting apparently has been conserved since life evolved.

"It's thought that RNA, or a molecule related to RNA, possibly were the first biomolecules, because they are capable of both performing work and carrying around their own genetic code," Golden said.

She and her research team used an intron from a bacteriophage, a molecule that attacks bacteria, to obtain an intron crystal structure trapped in the middle of the cutting and pasting cycle. As introns proceed through their work cycle, they change shape by folding and bending. By crystallizing the complex at various stages, the scientists can determine and study its three-dimensional structure and learn how it is able to carry out its biochemical work.

The Group I intron at its work cycle's mid-point, which Golden crystallized, is unreactive but reveals many of the interactions between the RNA and the molecules that it activates, she said.

"Knowing the structure can help us engineer molecules to behave better," Golden said. "It's very hard to find targets in cells because cells are organized in ways we still don't fully understand. This crystal structure shows us where the best targets are for modifying genetic defects."

The crystal structure of this Group I intron also will allow scientists to form models of hundreds of other introns in the same family and provide possibilities for new treatments for a wide variety of diseases, she said.

Other scientists now will use the information gleaned from this study in an attempt to develop new drugs, Golden said.

Introns were unknown until the late 1970s, and scientists are still investigating their function. Crystallization of the complex is one tool to determine their purpose.

Two intron structures in different stages of the cycle have been crystallized previously, and the targeted trans-splicing technique has been used to rep
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Source:Purdue University