All the genetic code required for the functioning of cells, tissues, and organs in our body can be found within genes. The process by which the information is read and executed, which resembles an assembly line, is called gene expression and is thoroughly regulated.
Thanks to an international team of scientists from Spain and Germany, we now know that there is a new step in the line, which controls the expression of some genes with an important role in cancer.
“We observed that breast cancer cells need a particular modification to express a set of genes required for cellular proliferation and tumour progression”, explained Priyanka Sharma, co-author of the paper. “This modification allows the enzyme RNA polymerase II to overcome a pausing barrier and to continue to transcribe these genes”.
With cancer, the mutated cells have a high tendency to proliferate, so the genes involved in cell division are really active and usually highly expressed. The mechanism which controls this complex system involves many different molecules to properly function. Even though the polymerase is ready, it still needs a final modification in order to begin transcription and be executed.
“We are now able to better understand how an intricate mechanism of gene regulation actually works and this might be a new target for clinical researchers to study novel therapies for certain types of cancer”, noted Miguel Beato, group leader, and principal investigator.
Their study outlines the changes happening in the Carboxyl terminal domain of RNA Polymerase II, namely the deimination of an arginine, by the enzyme PADI2. This allows the polymerase to transcribe genes relevant for cancer cell growth.
While most chemotherapies focus on blocking the activity of enzymes, these findings show that PADI2 functions in many different processes involving the nervous system, immune response and inflammation. Inhibiting PADI2 produces more side effects than previously known. The new approach makes possible the targeting of just the particular action of PADI2 on RNA polymerase needed for tumor progression without globally blocking the enzyme.
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