Yale Researcher Catches DNA in Act of "Scrunching"

The answer to how RNA polymerase stays still and moves at the same time while beginning its job of copying DNA into RNA is, according to a Yale scientist: “scrunching.”

Using x-ray crystallography, Professor Thomas Steitz, the Eugene Higgins Professor of Molecular Biophysics and Biochemistry at Yale, said he and Graham Cheetham, a post doctoral fellow working with him at the time, saw the movement.

“What we have is a DNA dependent RNA polymerase caught in the act of transcribing a gene,” said Steitz, whose findings were published Friday in the journal Science. “This answers the question of how the enzyme manages not to move, and yet, at the same time, go down the template.”

He said that, before his finding, there were two theories on how the action took place. In the first model, the RNA polymerase was believed to act like an inchworm, extending and expanding down the template. In the second model, one he calls “scrunching,” the enzyme did not change its structure, yet the DNA accumulates in the active site.

What Steitz and Cheetham observed was “scrunching.”

“We certainly saw things the rest of the field didn’t expect to see,” Steitz said. “These are the first insights into how RNA polymerase initiates transcription and how the transcription is regulated.”

DNA is the genetic material of most organisms. RNA, like DNA, also can hold genetic information. RNA is also the agent for transferring information from DNA to ribosomes, which are the protein synthesizing machinery of cells.

In that initial phase of transferring information, the enzyme RNA polymerase makes short transcripts eight or 10 nucleotides in length. Steitz said that it is during this phase that the RNA polymerase is bound to the promoter DNA and yet seems to move down the template.

“What we have is a view of the enzyme copying the DNA into RNA,” he said. “We have a crystal structure of the enzyme at the initiation of the transcription with the enzyme bound to a promoter DNA. That’s the signal of where to start the copying. We also have the structure of an initiation complex after the enzyme has synthesized a tri-nucleotide RNA. We can actually see the dynamic process from these two snapshots and understand what’s happening.”

Steitz and Yale Chemistry Professor Peter Moore in late summer published a study in the journal Nature that described their success in producing three-dimensional images of the largest component of the ribosome at a resolution high enough so that its parts could be identified and positioned.

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