Bruno Sargueil
Faculté de Pharmacie
Structure et traduction des ARN viraux
Website: https://www.citcom.cnrs.fr/
ORCID: 0000-0003-4483-355X
- General Scientific interests
We are interested in understanding the influence of viral RNA structure on their translation.
In this trend we studied internal ribosome entry in different viruses and more specifically in HIV. By reconstructing the translation initiation in vitro we have notably discovered a new translation initiation mode in HIV, modeled the atomistic structure of HCV viral RNA bound to the ribosome, and characterized new molecular mechanistic features for picornavirus translation.
To be able to model RNA structure and its dynamic as accurately as possible we are also involved in projects aiming at developing methods and software to predict RNA structure. For instance, in collaboration with a computer scientist team led by Y. Ponty (LIX – Ecole Polytechnique) we have developed an innovative integrative workflow to predict RNA secondary structure.
The main current projects aim at:
- Developing a method to map RNA modification at the genomic (Collaboration M. Etheve-Quelquejeu – UPCRS UMR8601) – Determining the effect of base methylation on RNA structure. Evaluate the effect of RNA methylation on HIV life cycle
- Developing methods to better predict RNA secondary and 3D structure. This includes molecular dynamics simulation and theoretical physics and chemistry to study RNA-ligands interactions
- Understanding the influence of the human RNA helicase DDX3 on HIV translation
- Technology available for other teams
We have developed a strong expertise in RNA structure modelling from experimental data. Both the experimental and the analytical steps are now mostly automated. Such process are also applicable to the study of RNA interaction with proteins or small molecules and may include docking studies. This technology is available for other teams.
Top 5 publications
1. Berta, D., Badaoui, M., Martino, S.A., Buigues, P.J., Pisliakov, A.V., Elghobashi-Meinhardt, N., Wells, G., Harris, S.A., Frezza, E., and Rosta, E. (2021). Modelling the active SARS-CoV-2 helicase complex as a basis for structure-based inhibitor design. Chem Sci 12, 13492–13505. https://doi.org/10.1039/d1sc02775a.
2. De Bisschop, G., Ameur, M., Ulryck, N., Benattia, F., Ponchon, L., Sargueil, B., and Chamond, N. (2019). HIV-1 gRNA, a biological substrate, uncovers the potency of DDX3X biochemical activity. Biochimie 164, 83–94. https://doi.org/10.1016/j.biochi.2019.03.008.
3. Deforges, J., de Breyne, S., Ameur, M., Ulryck, N., Chamond, N., Saaidi, A., Ponty, Y., Ohlmann, T., and Sargueil, B. (2017). Two ribosome recruitment sites direct multiple translation events within HIV1 Gag open reading frame. Nucleic Acids Res 45, 7382–7400. https://doi.org/10.1093/nar/gkx303.
4. Saaidi, A., Allouche, D., Regnier, M., Sargueil, B., and Ponty, Y. (2020). IPANEMAP: integrative probing analysis of nucleic acids empowered by multiple accessibility profiles. Nucleic Acids Res 48, 8276–8289. https://doi.org/10.1093/nar/gkaa607.
5. Willcocks, M.M., Zaini, S., Chamond, N., Ulryck, N., Allouche, D., Rajagopalan, N., Davids, N.A., Fahnøe, U., Hadsbjerg, J., Rasmussen, T.B., et al. (2017). Distinct roles for the IIId2 sub-domain in pestivirus and picornavirus internal ribosome entry sites. Nucleic Acids Res 45, 13016–13028. https://doi.org/10.1093/nar/gkx991.
Dernières publications sur HAL :
- [hal-04294940] Traceless Staudinger Ligation to Access Stable Aminoacyl- or Peptidyl-Dinucleotideby ano.nymous@ccsd.cnrs.fr.invalid (Camélia Kitoun) on 20 November 2023 at 10h52
Aminoacyl-and peptidyl-tRNA are specific biomolecules involved in many biological processes, from ribosomal protein synthesis to the synthesis of […]
- [hal-04294884] Designing molecular RNA switches with Restricted Boltzmann machinesby ano.nymous@ccsd.cnrs.fr.invalid (Jorge Fernandez-De-Cossio-Diaz) on 20 November 2023 at 10h45
Riboswitches are structured allosteric RNA molecules capable of switching between competing conformations in response to a metabolite binding event, […]
- [hal-04275415] Polypyrimidine-Tract-Binding Protein Isoforms Differentially Regulate the Hepatitis C Virus Internal Ribosome...by ano.nymous@ccsd.cnrs.fr.invalid (Jenniffer Angulo) on 8 November 2023 at 14h40
Translation initiation of the hepatitis C virus (HCV) mRNA depends on an internal ribosome entry site (IRES) that encompasses most of the 5′UTR and […]
- [hal-03775296] sRNA-controlled iron sparing response in Staphylococciby ano.nymous@ccsd.cnrs.fr.invalid (Rodrigo Coronel-Tellez) on 12 September 2022 at 14h23
Staphylococcus aureus, a human opportunist pathogen, adjusts its metabolism to cope with iron deprivation within the host. We investigated the […]