In yeast, the enzyme that transcribes the protein-making instructions encoded in DNA consists of roughly 30,000 atoms. Five years ago, Roger D. Kornberg published a solo portrait and an action shot of this molecular machinery in atomic detail.
Last week, Kornberg, of the Stanford University School of Medicine, was awarded the 2006 Nobel Prize in Chemistry for those images, which were the product of nearly 2 decades of research in his laboratory on the enzyme called RNA polymerase.
Working out the structure of RNA polymerase was “a marvelous achievement,” says James T. Kadonaga, a biochemist at the University of California, San Diego. “It’s one piece of a much larger puzzle, but an extremely important piece.”
The structure of RNA polymerase intrigued Kornberg because this enzyme begins the protein-making process. It copies gene sequences from DNA to create a single-stranded nucleic acid called messenger RNA. Other parts of the cell then use the messenger RNA to direct protein assembly.
To determine the enzyme’s structure, Kornberg and his colleagues used RNA polymerase from yeast cells. One of the many challenges in their work, says Kornberg, was developing the procedures to grow sufficient quantities of pure, three-dimensional crystals of RNA polymerase, which is a complex of 12 proteins.
Advances in X-ray crystallography, which the team used to image the enzyme, were also critical. In this technique, a sample scatters X rays that researchers had focused on it. From characteristics of the scatter, a computer creates an image showing the positions of the structure’s atoms.
The work of Kornberg’s team culminated in 2001 with two publications, one showing inactive RNA polymerase and the other capturing the machinery during the transcription process. The latter image shows how RNA polymerase grasps DNA and how the enzyme chooses the correct building blocks for the messenger RNA. It’s a picture that “I regard as one of the most indelible of our work,” says Kornberg.
Jeremy M. Berg, director of the National Institute of General Medical Sciences in Bethesda, Md., says, “If you understand the structure and the mechanism of how RNA polymerase works, it will help you understand gene regulation,” which in turn is “hugely important” to studies of disease.
The work by Kornberg and others has provided “significant” insights, says Richard H. Ebright of Rutgers University in Piscataway, N.J. He adds, “Most people in our field imagined [a Nobel prize on transcription] would be shared.”
“Transcription is a very large field,” says Kadonaga. “While I’m really happy for Roger [Kornberg], I also hope there is a place for other people, like Robert Roeder” of Rockefeller University in New York City, who discovered that there are multiple forms of RNA polymerase. “They are very deserving,” Kadonaga says.
