07.02.2012 / A molecular speed camera for RNA. Researchers at the ICGEB in Trieste have discovered that the RNA transcription speed can be very high

The mechanism involved in the transcription of genetic information from DNA to RNA through RNA polymerase enzyme activity has been known for some time. It has been discovered that this mechanism operates at a speed up to 10-20 times faster than that measured to date. The discovery was made by a group of researchers at the International Centre for Genetic Engineering and Biotechnology (ICGEB) in Trieste, headed by Alessandro Marcello, in partnership with the physicist Paolo Maiuri.

The prestigious magazine EMBO reports made this the cover story of its December issue. The Italian team examined the HIV virus, the pathogen that causes AIDS, which is integrated within the genome of the infected cell and uses the cellular RNA polymerase to transcribe its own genome. By using the fluorescence microscopy method for the first time, which makes it possible to observe the transcription process in live cells, the researchers were able to measure the speed of the polymerase on the HIV genome in real time. The result? The measurements obtained were 10-20 times faster than those measured using other techniques.

The method works like a sort of ‘molecular speed camera’: by tracing the build-up of RNA transcribed by the virus genome in the cell nucleus and then ‘switching off’ the fluorescence on the transcription site, the researchers were able to calculate how long it took for a new transcription to be completed, to the point at which balance was restored in the cell. The mathematical analysis of these measurements makes it possible to calculate the speed of the polymerase.

 “Transcription is a fundamental process closely controlled by the cell,” explains Alessandro Marcello, Group Leader of the Molecular Virology Laboratory at ICGEB. “Our measurements indicate that the speed of the polymerase may also be an important factor in regulating gene expression. Let’s take dystrophin for example, the longest known gene, the lack of which causes muscular dystrophy: until today it was estimated that a good sixteen hours were needed for a single transcription cycle, a very long time, which increases the risk of not completing the process. However, according to the new polymerase speed measurements, the time needed for the transcription of dystrophin is much lower, greatly reducing the risk of not completing the transcription of an essential gene.”
The next step for the researchers might be directed at gaining an understanding of the factors on which the RNA transcription speed depends, investigating, for example, whether the polymerase is modulated by a molecular accelerator or the morphological context of the cell. In fact, like a car, the speed also depends on the straightness or otherwise of the route and the obstacles in its path which, in the case of polymerase, are represented by DNA and protein packaging in the chromatin. Once all the factors that influence the process have been ascertained, it could be possible to see whether any alterations in the transcription speed can be associated with pathologies such as genetic diseases or cancer.
“Changing the scale of a simple measurement of a molecular process has many implications, including pathogenic ones. Basic research is responsible for understanding the mechanisms that could then be targeted by new therapeutic approaches,” concludes Marcello.

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