CM – How to make proteins at the right speed


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August 30, 2021

from the University of Geneva

In all eukaryotic organisms, genetic material is stored in the cell nucleus in the form of DNA. In order to be used, this DNA is first transcribed into messenger RNA in the cytoplasm of the cell and then with the help of ribosomes, small machines that are able to decode messenger RNA, in order to synthesize the corresponding proteins , translated into protein. However, the speed at which this mechanism takes place is not uniform: it has to adapt so that the protein can assume the correct configuration. Indeed, deregulating the rate of production leads to structural defects. The incorrectly folded proteins aggregate, become unusable and often toxic for the cell. By analyzing the ribosome movement in yeast cells, a team from the University of Geneva (UNIGE), Switzerland, in collaboration with the University of Hamburg, has succeeded in showing that the speed of protein synthesis is modulated by regulatory factors, which is the translation rate of messenger- RNA into proteins. These results can be found in the journal Cell Reports.

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Proteins are 3D structures that, in order to be effective, have to interlock with one another or interact with partners. If there is a structural defect, the proteins clump together, become toxic and potentially pathological. This phenomenon is actually observed in many neurodegenerative diseases, such as Alzheimer’s disease or amyotrophic lateral sclerosis. « We already knew that the speed at which proteins are produced varies as required: sometimes quickly, sometimes very slowly, » explains Martine Collart, professor at the Department of Microbiology and Molecular Medicine at UNIGE’s Medical Faculty Research conducted. « However, we did not yet know how this mechanism was controlled. »

To understand this process, the scientists used a very innovative and as yet unknown technique: ribosome profiling. « With this method, it is possible to determine the position of ribosomes at a specific point in time in the cell, » explains Olesya Panasenko, researcher in Martine Collart’s laboratory and head of the core facility ‘BioCode: RNA to Proteins’ at the Faculty of Medicine. who specializes in this technique. “It consists of breaking down all of the RNA that is not protected by the ribosome at a given point in time in order to keep only the ribosome-protected fragments (RPFs). We then sequence these RPFs to define how many ribosomes were on the mRNA. and at what positions, at that particular moment. This indicates the speed and efficiency of the translation. « 

The scientists observed the speed and dynamics of protein production in both natural yeast cells and genetically engineered yeasts in order to identify possible differences depending on the genetic code. During synthesis, in The cell has small condensates of RNA and proteins that have the function of slowing down ribosome production. « The formation of these condensates depends on the presence or absence of regulatory factors, the so-called distress, which act as retarders, » explains Martine Collart it accelerates the mechanism in the wrong places and leads to aggregated proteins.

Thus, emergency factors associate with the ribosome at certain times during protein synthesis in order to slow the ribosome during translation by condensing the RNA and the resulting protein . “One can wonder whether this Regul ation mechanism is impaired in neurodegenerative diseases or in old age, ”ask the authors. It is therefore possible that small perturbations, when they add up, have a significant cumulative effect over time.

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Similar title :
How to make proteins with the right one Producing speed
How to produce proteins at the correct speed


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