Friday, June 30, 2006

Genetic Transcription Pauses- Discarding randomness

A Stanford University news report offers insight as to why RNA polymerase pauses during the transcription process. Some general information from the first two paragraphs of the article:

"Of the thousands of proteins produced in our cells, few are as important as the enzyme RNA polymerase (RNAP), which has the unique ability to faithfully copy genetic information from DNA. In fact, all organisms—from bacteria to people—depend on RNAP to initiate the complex process of protein synthesis. Despite its crucial role in cell biology, fundamental questions remain about how the RNAP enzyme actually works.

Now scientists from Stanford University and the University of Wisconsin-Madison have solved part of the puzzle. Writing in the June 16 edition of the journal Cell, the research team found that a molecule of RNAP makes frequent pauses at specific sites along the DNA double helix. This finding comes on the heels of the team's 2003 discovery that RNAP enzymes routinely make thousands of brief stops ("ubiquitous pauses") when carrying out the vital task of transcribing genetic information from DNA to RNA—a process called transcription."

[Bradford]: The author gets to the meat of the matter later in the article.

"That's great," Block said. "It's telling us that the enzyme is doing just what it should. After all, it's seen the same sequence eight times in a row, so it had better do the same thing eight times in a row. It also paused at several other sites as well, which is interesting. Sometimes it paused longer, sometimes shorter, but the average was remarkably the same—about a second or so. We also discovered that it just didn't stop at any old sequence but at very specific places where there's a signal in the DNA that basically says, 'Pause here.'"

That signal, he added, occurred for specific sequences in the DNA. "We found that there is always a G near a specific pause position, and always a T or a C at another nearby position," he said. "So the pause seems to be sequence dependent. It's not always the same duration every time, but it's more likely to pause at one of these sites than at any other sites in between, so it's not just some random phenomenon that happens every once in a while. If I'm running down the road and I trip, that would be a random phenomenon. But if I run down the road and every time I trip there's a pothole, then that's not random."

Some researchers have argued that all pauses might be associated with either hairpin formation or backtracking, but the Cell study contradicts that assumption. "Most ubiquitous pauses have nothing whatsoever to do with backtracking or hairpins," Block said. "We think ubiquitous pauses are the most common and probably most important kind of pause, and the models that some biochemists have been using are just wrong."

[Bradford]: So pauses seem to be sequence dependent and not random. Removal of randomness as a causal agent when knowledge of actual causation comes to light is a familiar theme. More knowledge of genomic dynamics should dispel other ideas grounded in ignorance like the belief that unknown function equates to "junk DNA."


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