Bruno Sargueil

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.

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