Resolving the Structure of a Guanine Quadruplex in TMPRSS2 Messenger RNA by Circular Dichroism and Molecular Modeling

D'Anna, L.; Froux, A.; Rainot, A.; Spinello, A.; Perricone, U.; Barbault, F.; Grandemange, S.; Barone, G.; Terenzi, A.; Monari, A.

doi:10.1101/2024.07.29.605618

bioRxiv · 10.1101/2024.07.29.605618

Resolving the Structure of a Guanine Quadruplex in TMPRSS2 Messenger RNA by Circular Dichroism and Molecular Modeling

D'Anna, L.·Froux, A.·Rainot, A.·Spinello, A.·Perricone, U.·Barbault, F.·Grandemange, S.·Barone, G.·Terenzi, A.·Monari, A.

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Abstract

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.

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D'Anna, L., Froux, A., Rainot, A., Spinello, A., Perricone, U., Barbault, F., Grandemange, S., Barone, G., Terenzi, A., Monari, A.. 2024-07-30. Resolving the Structure of a Guanine Quadruplex in TMPRSS2 Messenger RNA by Circular Dichroism and Molecular Modeling. https://doi.org/10.1101/2024.07.29.605618

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