Competition of RNAs for RNase E, a mechanism regulating their degradation and the energy and carbon metabolisms in the cell. – RECOM
Biotransformation capacities of cells are directly linked to cellular metabolism. The enzymatic process of RNA decay participates to metabolism regulation by controlling gene expression post-transcriptionally. Thousands of RNA molecules belonging to three classes (messenger, ribosomal and transfer RNAs) are prone to be degraded at the same time in cells and compete for enzymes of the degradation machinery. This competition mechanism and the impact of such competition on cell activity have not been previously studied. In the RECOM project, we will characterize for the first time the substrate/enzyme competition mechanism in vivo when thousands different RNAs compete for RNase E binding, the enzyme responsible for the initiation of RNA decay in E. coli. An approach of in vivo enzymology will be developed. Perturbations of the two kinetics partners, the substrates or the enzyme, in the cells using a series of targeted mutants will be performed in vivo and apparent kinetic parameters of RNase E for all RNAs, will be estimated by modelling. By exploring genome-wide RNA stability, the project will challenge the dogma of stable and unstable RNAs. In order to quantify how the RNA competition for decay affects E. coli cell activity, energy and carbon metabolisms will be thoroughly characterized by the measurement of growth, accumulated metabolites and intracellular quantitative multi-omics data. The project will reveal the cellular trade-off for intracellular resource allocation between RNA decay, carbon and energy metabolisms and thus provide the first comprehensive view of bacterial metabolism integrating the interconnections between these three metabolisms. This new vision of the mechanisms governing bacterial life could also open the way to new strategies in biotechnology based on the modulation of RNA decay for cellular activity optimization.
The RECOM project deals with the fundamental principles of biochemistry/microbiology. Due to the novelty of the approach, large scientific impacts are expected in the short, medium or long term, in enzymology, bioenergetics, microbial metabolism and modelling. In addition of these scientific impacts in basic and disciplinary research, major economic and social impacts are expected in the longer term due to the identification in the work program of promising strategies for the optimization of bacterial activity for application in biotechnology and synthetic biology.
Project coordination
Muriel COCAIGN-BOUSQUET (Toulouse Biotechnology Institute)
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
Partner
TBI Toulouse Biotechnology Institute
Inria GRA Centre Inria de l’Université Grenoble Alpes
Help of the ANR 450,522 euros
Beginning and duration of the scientific project:
February 2024
- 48 Months