The team BLADE a analysé comment la cellule bactérienne réagit face à un accident de la traduction pour mieux comprendre le processus biologique du contrôle qualité des ARNm.
In the bacterium Escherichia coli, when translation elongation is prematurely halted and part of the molecule is no longer covered by ribosomes, mRNA is homogeneously destabilized, even though mRNA molecules are heterogeneous and of different lengths. This result showed that not all non-functional mRNA molecules are destroyed, revealing the wasteful use of intracellular resources and shedding new light on mRNA quality control in bacteria.
mRNA is a central molecule in gene expression. Produced by gene transcription, it is the molecular template for transforming genetic information into protein through translation. mRNA is a highly unstable molecule, rapidly degraded by a series of RNases present in the cell.
The team has developed a strategy for measuring stability along the entire length of the mRNA molecule. Using a set of specific probes, it is now possible to determine the stability parameters and local concentrations of different portions of a molecule, to determine whether a molecule is homogeneously degraded or whether certain portions are more stable (or less stable) than others.
In Escherichia coli, this mapping has shown that when translation elongation is stopped prematurely and part of the molecule is no longer covered by ribosomes, the mRNA is homogeneously destabilized. This destabilization is mainly due to an enzyme (RNase E) and its ability to form a complex with other proteins (degradosome). On the other hand, we discovered heterogeneity at the level of the mRNA molecules, which can present different lengths in the cell. This result revealed that not all non-functional molecules are destroyed, shedding new light on mRNA quality control in bacteria, which does not result in total degradation of these molecules.
The quality control of mRNAs contributes to the proper functioning of the cell by avoiding the expression of unnecessary functions that waste intracellular resources. The TBI team is now focusing its research on characterizing the players involved in mRNA quality control mechanisms, with the aim of gaining a better understanding of this molecular heterogeneity and, ultimately, better controlling it. Controlling mRNA degradation is a lever for optimizing the expression of genes of interest. This research will also have an impact on the construction of high-performance bacterial chassis for biotechnology.
Valorization
Duviau MP, Chen F, Emile A, Cocaign-Bousquet M, Girbal L, Nouaille S. 2023. When translation elongation is impaired, the mRNA is uniformly destabilized by the RNA degradosome, while the concentration of mRNA is altered along the molecule. Nucleic Acids Res. 2023 Feb 25. DOI: 10.1093/nar/gkad104.
Contact TBI
Muriel Cocaign-Bousqeut et Sébastien Nouaille cocaign@insa-toulouse.fr et sebastien.nouaille@insa-toulouse.fr
