Not4 and 5 Found to Regulate Protein Synthesis Rate

By analyzing the rate of ribosome movement in yeast cells, a team from the University of Geneva, in collaboration with the University of Hamburg, has succeeded in demonstrating that protein synthesis rate is modulated by Not regulatory factors, that modify the rate of translation of messenger RNA into proteins at will. These results were published in Cell Reports.

“We already knew that the rate at which proteins are made varies according to need: sometimes fast, sometimes very slow," explains lead researcher Martine Collart. “However, we did not yet know how this mechanism was controlled.”

In order to understand this process, the scientists used ribosome profiling. “This methodology makes it possible to determine the position of ribosomes at a given moment in the cell,” explains collaborator Olesya Panasenko. “It consists of degrading, at a specific moment, all the RNA that is not protected by the ribosome, to keep only the ribosome-protected fragments (RPFs). We then sequence these RPFs in order to define how many ribosomes were on the mRNA, and at which positions, at that particular moment. This indicates the speed and efficiency of translation.”

The team observed the speed and dynamics of protein production in natural yeast cells as well as in genetically modified yeast, in order to identify possible differences depending on the genetic code. During synthesis, small condensates of RNA and proteins appeared in the cells, with the function of slowing down the rate of ribosome production. “The formation of these condensates depends on the presence or absence of regulatory factors, called Not, which act as decelerators,” explains Collart. In their absence, the mechanism accelerates in the wrong places and results in aggregated proteins.