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07Apr 2017

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NKI researchers find a link between DNA transcription rate and translation efficiency

Our cells - and ultimately our entire body - are governed by genes, the functional units of our DNA. Gene expression rests on two very important processes, called transcription and translation. These two processes were thought to function independently. But the research group of Reuven Agami from the Netherlands Cancer Institute (NKI) now shows that there is indeed a link between them. The group's work was published in the journal Cell on April 6.

DNA Rechtenvrij

During gene expression, first, the DNA is 'read' and the gene is copied into a string of RNA. This is called transcription. Next, this piece of RNA moves outside the cell nucleus (where our DNA is located), and cell structures called ribosomes use it as a template to make a protein. This process is called translation. These two processes where thought to be independent. They are governed by different cell structures, and on top of that they take place at different locations within the cell. Reuven Agami's team has now found proof that there is indeed a link between the two: the faster the rate of transcription, the more efficiently the RNA's are translated into proteins.

"There already were some indications that this such a connection might exists", comments Agami. "We managed to demonstrate it and to show how it works. We tried different things, for instance, artificially increasing the amount of RNA of certain genes. Because maybe the mechanisms is just that the more RNA is present, the more efficiently it gets translated into proteins. But no, this turned out to not be true."

How does it work then? Through epigenetics. Epigenetics is the term used for all types of modifications that influence our genes, other than actually changing the code of the DNA. A common type of epigenetic mechanism is methylation. When a methyl group is added to RNA in the coding region, it acts as a kind of concealing tape that reduces the efficiency of reading that piece of genetic code. "We observed that the faster the DNA is transcripted, the less likely the RNA is to be methylated. Which has a positive effect on the RNA translation, resulting in more proteins", says Agami.

This important fundamental new insight doesn't have any applications yet. Though it could mean that in the future we might influence gene expression by modifying the methylation process. But it is fascinating to see how much we still have to discover when it comes to DNA and the way our genetics works. 

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