ARN UPR 9002 — Laboratory

RNA Structure and Reactivity

Headed by Roland Marquet

    Presentation

    The RNA Structure and Reactivity intramural research unit (Architecture et réactivité de l'ARN – UPR 9002) is composed of 12 teams that share common objectives centred on the role of RNA in viral infections (coronaviruses, retroviruses, influenza viruses, arboviruses, herpesviruses, etc.), bacterial infections (S. aureus, C. diff, S. flexneri) and parasitic infections (P. falciparum). Our teams are as interested both in the fundamental mechanisms of pathogen replication as they are in host-pathogen relationships and host defence mechanisms.

    RNAs, which are involved in countless cellular processes, play key roles in all of these mechanisms. RNA structures control various biological processes through selective and specific interactions that we are still a long way from understanding and whose study opens up many fundamental and practical opportunities, including mRNA vaccines.

    To address the structure-function relationships of RNAs, we draw on the multi-disciplinary skills of researchers in structural, cellular and molecular biology, bioinformatics, chemistry and biophysics. The unit has innovative equipment (a biophysical platform to study molecular interactions, mass spectrometry to characterise RNA modifications, etc.) and is developing cutting-edge methods to analyse RNA structure and function (biochemical approaches coupled with high-throughput sequencing, microfluidic infrastructures applied to RNA evolution and imaging, etc.).

    Research topics

    Structure, dynamics and targeting of biomolecular machines

    Biophysical and structural studies related to RNA in the fight against antibiotic resistance, the Zika and Dengue viruses, as well as the identification of new RNA targets in cancers.

    Evolution of translation initiation systems in eukaryotes

    Studying the regulatory elements of translation initiation of cellular and viral mRNAs, including the hypermethylated cap. Initiation abnormalities leading to neurodegenerative pathologies (ALS, etc.).

    Post-transcriptional regulation and nutrition

    Analysis of the biological mechanisms by which antioxidant dietary supplements, particularly selenium, promote resistance and adaptation to biotic and abiotic stress.

    RNA encapsidation and viral assembly

    Selection and encapsidation of genomic RNAs from retroviruses, influenza A viruses and coronaviruses: the roles of RNA-RNA and RNA-protein interactions. Restriction factors of HIV-1 (APOBEC3G and 3F).

    Bacterial pathogenesis and immunity

    Analysis of the role of oxygen in host-pathogen interactions involving Shigella flexneri as a model system, and analysis of bacterial adaptation mechanisms during infection.

    Retroviruses and molecular evolution

    Development of new viral vectors for biomedical applications based on molecular evolution approaches. Evolutionary mechanisms of HIV.

    RNA-mediated regulation of viral infections

    Analysis of host-virus interactions in humans, in particular the interaction of the innate immune response with the microRNA machinery and RNA interference

    Molecular virology

    HIV-1 reservoirs and persistence. Long non-coding RNAs and antiviral response. Epidemiology of emerging pathogens in wastewater.

    RNA regulation in pathogenic bacteria

    Translation, epitranscriptome and regulation by RNAs in response to various forms of stress and during infection.

    Major events and works

    Conference organisation

    • Co-organisation of Applied Biophysics Forum in Drug Delivery, 27-28 May 2024, Copenhagen (E. Ennifar)
    • Co-organisation of Biophysics of RNA-LNPs and non-viral vectors, 1 June 2023, Stockholm (E. Ennifar)
    • Organisation of the first French-German Young Crystallographers' Meeting, 26-29 September 2023 (C. Sauter)
    • Co-organisation of the international congress "RNA in gene control across kingdoms", 2-5 May 2022, Bischenberg (P. Romby, M. Frugier, S. Pfeffer, M. Ryckelynck)

    Platform

    • INSTRUCT-ERIC labelling of the advanced microcalorimetry platform, 2022 (E. Ennifar)

    Publications

    • Baldaccini et al, EMBO J 43, 806, 2024
    • Bahena-Ceron et al, RNA 30, 200, 2024
    • Compain et al, JACS Au, 4, 432, 2024
    • El Soufi et al, Water Res. 249,120959, 2024
    • Husser et al, Small, 19, e2205232, 2023
    • Tardivat et al. Nucleic Acids Research 51,8673, 2023
    • Toccafondi et al, PLoS Pathog 19, e1011207, 2023
    • Skerniskyte et al, Gut Microbes, 15, 2271597. 2023
    • Wolff et al, RNA 29,551, 2023
    • Jakob, Paul Stansilaus et al, Nucleic Acids Research, 50, 9023, 2022
    • Verdikt et al, EBioMedicine 79, 103985, 2022
    • Westhof et al, Nucleic Acids Research 50, 4100, 2022
    • Chameettachal et al, Nucleic Acids Research, 49, 4668, 2021
    • Montavon et al PLOS Pathogens 17, e1009549, 2021
    • Vilimova et al, Nucleic Acids Research 49,10018, 2021
    • Bouhedda et al, Nature Chemical Biology, 16, 69, 2020
    • Chernorudskiy et al, PNAS 117, 21288-21298, 2020
    • Georg, Lalaouna et al, Mol Microbiol, 113, 603, 2020
    • Kanja et al, J Virol, 94:e01035-20, 2020
    • Kruse et al, Angew Chem Int Ed Engl, 59, 16553, 2020
    • Lopez et al, J Virol 94, e02145, 2020
    • Orlov et al, PNAS 117, 10848, 2020

    Patents

    • Three patents (2020, 2022, 2024) protecting new therapeutic strategies targeting antibiotic-resistant bacteria
    • A patent protecting sensitive detection of bacteria in microfluidic droplets, 2022

    Commercialisation and technology transfer

    • Commercialisation of the CrystalChip by the Idylle start-up, 2023
    • Creation of the MicroOmix S.A.S. start-up, 2021

    Practical information