Scientists have taken the most detailed images yet of an enzyme working its way along a strand of DNA, revealing how it reads the genetic code. The enzyme RNA polymerase III is responsible for running along the DNA and producing a read-out in the form of RNA that the cell can use to make proteins. Finding out exactly how this happens can show how healthy cells perform this essential function, as well as hinting at ways to medically intervene when cells get it wrong.
A team at the Institute of Cancer Research (ICR) in London froze yeast samples at -180 C before imaging them using a form of electron microscopy called Cryo-EM. This incredibly powerful form of microscopy can take pictures on an almost atomic scale, showing molecules that are about one 20,000th the width of a human hair. RNA polymerase III was imaged frozen in the act of transcribing DNA, with the results published in the journal Nature.
'You don't get the structure all at once, you just see individual strokes and it takes a while to see the big picture,' study author Dr Alessandro Vannini told the BBC. 'It was definitely a Van Gogh.'
After obtaining more than a million snapshots of the enzyme at work, the team pieced the pictures together using powerful computers to visualise the 3D complex formed by the enzyme and the DNA strand.
The results show how all the parts of the RNA polymerase III complex fit together and interact with each other and the genetic code. The samples were yeast, but the basic process is very similar across all organisms. The team also hopes that the results could be used to find new drug targets for cancer. RNA polymerase III is overactive in cancerous cells, in order to produce the large quantities of protein for rapid cell division and growth. The images identified five key stages for transcription. Each one of these stages could provide novel targets for cancer therapies, the researchers say.
'This beautiful study has unveiled a fundamental cog in the inner workings of cells, and one that is often exploited by cancers,' said Professor Paul Workman, chief executive of the ICR. 'It's a hugely important finding in cell biology, and I hope that in future it will lead to new treatments for cancer patients.'