Team
Team manager: Redder Peter
Presentation
To survive, cells must regulate their protein production, and a major pathway for this is to regulate either synthesis and /or degradation of the mRNA. Our work focuses on the mechanisms of mRNA degradation/processing in the opportunistic pathogen Staphylococcus aureus, the leading cause of nosocomial infections.
mRNA half-lives in S. aureus are generally very short, with an average of less than a few minutes. The rapid turnover of mRNA is ensured by a set of highly efficient RNases, who nevertheless need to be kept under control to avoid fully depleting the mRNA pool in the cell.
S. aureus can switch between different lifestyles: Peaceful coloniser of the human naso-pharynx, aggressive pathogen or enter into an antibiotic-tolerant “persister” state. Each of these modes require a specific RNA expression profile, and transitions between these profiles necessitates precise control of the RNA decay.
Our team aims to understand how the S. aureus RNases target the correct RNA molecules, and how the RNA degradation is controlled to occur at the right time and with the right efficiency. How do the RNA decay enzymes work together? and how are their activities modulated when S. aureus changes lifestyle?
Project 1
Bulk mRNA degradation in S. aureus is primarily performed by RNase Y and the two paralogous ribonucleases RNase J1 and J2 (which are thought to form a J1-J2 complex).
One of the potential control points for RNase J1 5′-exoribonuclease activity is the conversion of 5′-tri-phosphorylated RNA into a preferred 5′-mono-phosphorylated RNA that can be performed by RNA pyrophosphohydrolases (RPPs). The S. aureus genome encodes five putative RPPs and we are determining the target range of each of those RPPs in order to correlate this to their effects on RNase J-mediated decay.
We have shown that key elements in the control of RNase Y are the sequences and secondary structures of the RNA substrates. However, the intracellular localization of both RNase Y and its substrates, as well as interactions with protein partners play an equally important role, which we are investigating.
Project 2
BASRae1 (collaboration with the Condon lab (Paris), the Giege lab (Strasbourg) and Gene-Wei Li (MIT, USA)).
The Ribosome associated endoribonuclease (Rae1) conserved in the Firmicutes and Cyanobacteria as well as in plants (where it localizes to the chloroplast). Rae1 has been shown to cleave mRNA in a translation and reading frame dependent manner in Bacillus subtilis, and the objectives of the BASRae1 project are to determine (i) the key features of ribosome stall signals and sequence determinants around the cleavage site required for efficient mRNA degradation by Rae1, (ii) how Rae1 interacts with the ribosome (iii) whether physiological conditions that provoke translational stress can induce Rae1 activity. This project will allow us to decipher the precise molecular mechanism of Rae1 recruitment to the ribosome, that may lead to ribosome rescue and the degradation of non-functional mRNA.
Project 3
Patho-TOX (collaboration with Patricia Bordes (CBI), Mathieu Bergé (CBI) & Lionel Mourey (IPBS)).
Toxin-antitoxin systems (TA) are major elements in the switch between persister state and normal growth. Rosmer-family TAs are found in several bacterial pathogens, and our team is investigating how this TA family is regulated in S. aureus, and what transcriptomic and physiological effect the Rosmer TAs have on the bacteria.
– Alexandre Le Scornet, Ambre Jousselin, Kamila Baumas, Gergana Kostova, Sylvain Durand, Leonora Poljak, Roland Barriot, Eve Coutant, Romain Pigearias,Gabriel Tejero, Jonas Lootvoet, Celine Pellisier, Gladys Munoz, Ciaran Condon, Peter Redder. Critical factors for precise and efficient RNA cleavage by RNase Y in Staphylococcus aureus.
– Boufafa M, Kadri S, Redder P, Bensouilah M. . Occurrence and distribution of fecal indicators and pathogenic bacteria in seawater and Perna perna mussel in the Gulf of Annaba (Southern Mediterranean). Environ Sci Pollut Res Int. 2021 Sep;28(33):46035-46052. 2021 Sep doi: 10.1007/s11356-021-13978-4.
– Guimarães VA, Le Scornet A, Khemici V, Hausmann S, Armitano J, Prados J, Jousselin A, Manzano C, Linder P, Redder P. . RNase J1 and J2 Are Host-Encoded Factors for Plasmid Replication. Front Microbiol. 2021 May 4;12:586886. 2021 May doi: 10.3389/fmicb.2021.586886. PMID: 34017314; PMCID: PMC8129170.
– Sierra R, Prados J, Panasenko OO, Andrey DO, Fleuchot B, Redder P, Kelley WL, Viollier PH, Renzoni A. Insights into the global effect on Staphylococcus aureus growth arrest by induction of the endoribonuclease MazF toxin Nucleic Acids Res. 2020 Sep doi: 10.1093/nar/gkaa617. PMID: 32735661; PMCID: PMC7470975.
– Trachsel E, Redder P, Linder P, Armitano J.. Genetic screens reveal novel major and minor players in magnesium homeostasis of Staphylococcus aureus PLoS Genet 2019 Aug
– Le Scornet A, Redder P. Post-transcriptional control of virulence gene expression in Staphylococcus aureus Biochim Biophys Acta 2019 Jul
Affiliation
