DISCOVERY OF A NEW REGULATORY MECHANISM
A potential tool for controlling the production of proteins
The Unité des Interactions Bactéries-Cellules (Bacteria-Cell Interaction Unit) of the Institut Pasteur, directed by Pascale Cossart, in collaboration with the Institut de Biologie Physico-Chimique (Institute of Physico-Chemical Biology), has just deciphered a molecular mechanism which explains how Listeria monocytogenes, the bacteria responsible for listeriosis, starts its infectious process in the host: it is entirely a question of temperature. The newly-discovered mechanism, published in Cell, could be an interesting tool in numerous areas of research and in industry.
Listeria monocytogenes is a bacterium responsible for a severe food-borne infection, listeriosis, which appears principally in industrialized nations. In Listeria monocytogenes, the infection involves the activation of genes, which allows it to engage the infectious process, then to survive and to multiply in the organism. These virulence genes are expressed maximally at 37°C (98.6°F), the temperature of the human host, while they are almost inactive at lower temperatures: this bacterium, like others, has thus adapted itself to begin its infectious process only when it encounters an organism at the "right" temperature.
The thermodependent mechanism which is at the root of this phenomena has just been discovered by researchers from the Institut Pasteur, who also demonstrated that it was transposable to other bacteria. This could be a useful tool for controlling the production of proteins.
Recall that proteins are produced from "messenger RNA" (mRNA) which direct messages encoded by the genes towards the machinery of the cell's protein synthesis. In short, a gene (a fragment of DNA that codes for a protein) is first transcribed in mRNA, then the mRNA is translated into a protein.
It was already known that the activation of virulence genes in Listeria monocytogenes was controlled by a protein, PrfA. The researchers demonstrated that at 20-30°C (68-86°F), the mRNA of this gene is produced, but equipped with a structure that prevents its translation into a protein. When the temperature is raised, this structure, called a "thermosensor," is destabilized, and at 37°C (98.6°F), the prfA-mRNA regains a normal configuration that allows the production of the protein (and thus the activation of the virulence genes).
In conclusion: the prfA-mRNA functions as a thermostat, and can thereby sense the temperature in the environment and direct the expression of virulence genes in a thermocontrolled fashion.
In terms of applications, the most interesting aspect is that the researchers from the Institut Pasteur showed that they could transpose this system to other bacteria that lack it. The experiment was carried out in Escherichia coli, and the production of a protein was made temperature-controllable by equipping the corresponding DNA of the coding part of the thermosensor (where the production of a thermodependent mRNA takes place).
It thus becomes theoretically possible to control the production of proteins according to the temperature in the bacterium. This would, for example, allow the prompting of the synthesis of a specific protein at a precise moment in an experiment-something that affects academic research. Certain bacteria are, moreover, used as "factories" for proteins (enzymes, proteins for medical purposes, etc.) in different industrial fields, and the thermosensor can facilitate a rapid and controlled production in time.
This project is a new example of the power of RNA regulation.
- "An RNA Thermosensor
Controls Expression of Virulence Genes in Listeria Monocytogenes" :
Cell, 6 septembre 2002.
Jörgen Johansson(1), Pierre Mandin(1), Adriana Renzoni(1), Claude Chiaruttini(2), Mathias Springer(2), Pascale Cossart(1)
1. Unité des Interactions
Bactéries-Cellules, Institut Pasteur, Paris
2. Institut de Biologie Physico-Chimique, Paris
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