Resolving the Structure of a Guanine Quadruplex in TMPRSS2 Messenger RNA by Circular Dichroism and Molecular Modeling
The presence of a guanine quadruplex in the opening reading frame of the messenger RNA coding for the transmembrane serine protease 2 (TMPRSS2) may pave the way to original anticancer and host-oriented antiviral strategy. Indeed, TMPRSS2 in addition to being overexpressed in different cancer types, is also related to the infection of respiratory viruses, including SARS-CoV-2, by promoting the cellular and viral membrane fusion through its proteolytic activity. The design of selective ligands targeting TMPRSS2 messenger RNA requires a detailed knowledge, at atomic level, of its structure. Therefore, we have used an original experimental-computational protocol to predict the first resolved structure of the parallel guanine quadruplex secondary structure in the RNA of TMPRSS2, which shows a rigid core flanked by a flexible loop. This represents the first atomic scale structure of the guanine quadruplex structure present in TMPRSS2 messenger RNA.
Authors
- Florent Barbault (ORCID: https://orcid.org/0000-0002-6082-3194)
- Aurane Froux (ORCID: https://orcid.org/0000-0002-8607-4806)
- Giampaolo Barone (ORCID: https://orcid.org/0000-0001-8773-2359)
- Stéphanie Grandemange (ORCID: https://orcid.org/0000-0002-4101-6303)
- Angelo Spinello (ORCID: https://orcid.org/0000-0002-8387-8956)
- Alessio Terenzi (ORCID: https://orcid.org/0000-0001-9751-1373)
- Luisa D’Anna (ORCID: https://orcid.org/0000-0002-7046-5140)
- Ugo Perricone (ORCID: https://orcid.org/0000-0002-2181-2468)
- Antonio Monari (ORCID: https://orcid.org/0000-0001-9464-1463)
- Aurianne Rainot (ORCID: https://orcid.org/0000-0002-1860-1096)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Université Paris Cité (FR)
- Sorbonne Paris Cité (FR)
- Centre de Recherche en Automatique de Nancy (FR)
- Interfaces Traitements Organisation et Dynamique des Systèmes (FR)
- Ri.MED (IT)
- University of Palermo (IT)
- Université de Lorraine (FR)
Publication Details
- Journal
- Chemistry - A European Journal
- Published
- 2024-10-04
- DOI
- https://doi.org/10.1002/chem.202403572
- Citations
- 2
- Primary Topic
- DNA and Nucleic Acid Chemistry
- Type
- article
- Field-Weighted Citation Impact
- 0.47
Funders
- Laboratoire d'Excellence SEAM
- European Commission
- Agence Nationale de la Recherche
- Grand Équipement National De Calcul Intensif