Role of RNA Polymerase II in Protein Synthesis Clarified

According to researchers at the University of Toronto, RNA polymerase (Pol) II drives generation of the building blocks of ribosomes. The discovery reveals a previously unknown function for the enzyme in the nucleolus, where the enzyme had not been seen before. Pol II is one of three RNA polymerases that together enable cells to transfer genetic information from DNA to RNA and then proteins.

"Our study redefines the division of labour among the three main RNA polymerases, by identifying Pol II as a major factor in the control of nucleolar organizations underlying protein synthesis," said Karim Mekhail, senior author of the paper published in Nature today. "It also provides a tool for other researchers to interrogate the function of certain nucleic acid structures more precisely across the genome."

Mekhail and his colleagues found that inside the nucleolus, Pol II enables the expression of ribosomal RNA genes—a key step in the creation of ribosomes. Pol II, they showed, generates R-loops—hybrid DNA-RNA structures—that directly shield ribosomal RNA genes from molecular disruptors called sense intergenic non-coding RNAs (or sincRNAs).

Those disruptors are produced by Pol I in intergenic, non-protein-coding sequences of DNA between genes, and they become more active in various conditions: disruption of Pol II, under environmental stress, and in Ewing sarcoma.

"Pol II puts the brakes on Pol I and prevents sincRNAs from 'sinking' the nucleolus," added Mekhail. "That's how we united the name and action of the disruptors in our discussions of this work."

Mekhail and his team also developed a new technology to test the function of R-loops at specific locations on chromosomes, which they dubbed the 'red laser' system. "The existing tool in the field would obliterate R-loops across the whole genome, but we wanted to test the function of R-loops associated with a given genetic locus," said Mekhail. "We were able to turn an old technology into a modern laser-guided missile, which we are still working to further improve."