Digging for genetic fossils: Hutchinson Center researchers solve structure of ancient biological molecule

Using an X-ray machine that accelerates particles close to the speed of light, scientists at the Fred Hutchinson Cancer Research Center have gotten a backward glimpse into primordial biology, capturing the dance of a genetic fossil in motion.

Their work, published today in Nature, is the first to capture the structure and choreography of an intricately folded ancient biological molecule as it twists and turns to carry out its enzymatic function. By solving the 3-D structure of the hairpin ribozyme, found in a virus that infects tobacco plants, lead author Adrian Ferr-D'Amar, Ph.D., and colleagues discovered that it is strikingly similar in function to the well-characterized ribonuclease A protein, whose structure was determined more than 30 years ago. Although these two enzymes are drastically different from a molecular standpoint, their jobs are the same: snipping RNA - an information-containing molecule similar to DNA - into smaller pieces.

"This was probably the biggest surprise of our study," said Ferr-D'Amar, an assistant member of the Hutchinson Center's Basic Sciences Division. "Both enzymes have to twist their RNA substrate in the same fashion in order to cleave it. Because the two enzymes are completely distinct, we'd say this is an example of convergent evolution - each independently evolved the same strategy to do the job, probably because there are limited ways to carry out this kind of chemistry."

Ferr-D'Amar's fascination with RNA stems in part from the theory that it may be the most ancient biological molecule. However, some present-day life forms, such as HIV and poliovirus also use RNA as their genetic material. "Cells need the ability both to store genetic information and to carry out specific functions through a chain of chemical events called catalysis," he said. "Modern cells use DNA for information storage and proteins for doing the catalytic work, but the primordial cell is thought to have used RNA for both processes. The ribozome

Contact: Kristen Woodward
Fred Hutchinson Cancer Research Center

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