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Angstrom-level Resolution Helps Solve RNAP Ladder Mystery

November 15, 2005 by Robert Desideri

Heh, until researchers at Stanford recently figured out an new implementation of optical force clamps, traditional optical trap resolution was insufficient to view activity in realtime at the molecular level. Upon sorting the problem and creating angstrom-level resolution (which is around the size of a hydrogen atom for those keeping score), they had a historical first look at how RNA polymerase (RNAP) does its stuff. Needless to say, this is very cool and a graduate student named William Greenleaf figured out the stabilisation scheme which enabled the nailing of the resolution.

Why is it so cool you ask, well, we now get to watch transcription in realtime, which is what the researchers did. From the Stanford announcement:

With these innovations in place, the research team appears to have settled some of the fundamental arguments over DNA-RNA transcription. “Quite simply, our experiment rules out both discontinuous-location models,” Block says. “Neither the inchworm nor the scrunching model is consistent with our data, and the idea that some have held all along—that RNAP climbs the DNA ladder one base pair at a time—is probably the right answer.”

The Stanford group also weighed in on another controversy concerning the actual mechanism that allows RNAP to advance. “RNAP is a molecular motor that starts at one end of the DNA and walks down to the other end,” Block explains. “It gets its energy from the chemical reaction that occurs when it copies A, T, G or C. It’s as if a machine that lays down asphalt could somehow be powered by the asphalt itself.”

Yeah it’s still unknown what powers the RNAP up the ladder but it narrows the investigation now knowing with more certainty the one base pair at a time answer. Wow, we’ll soon understand better how such motor enzymes work. Awesome.

Imagine the avalanche of experiments and investigations now on the immediate horizon. Think about how many researchers are ready for a closer look at things like how virus-encoded helicases do their business, protein folding, DDX3 curiosities and all sorts of other transcription-related diagnostic and therapeutic related research. Holy mackerel, this is bigger than PCR (not to diminish that invention), this is the kind of news that makes one want to be a researcher – or at least a life sciences VC.

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