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Molecules 2018, 23(12), 3124; https://doi.org/10.3390/molecules23123124

In Cellulo Protein-mRNA Interaction Assay to Determine the Action of G-Quadruplex-Binding Molecules

1
Université Paris 7, Inserm, UMR 1162, 75013 Paris, France
2
ICCVS, University of Gdańsk, Science, ul. Wita Stwosza 63, 80-308 Gdańsk, Poland
3
Chemistry, Modelling and Imaging for Biology, CNRS UMR9187-Inserm U1196, Institut Curie, Université Paris-Sud, F-91405, Orsay, France
4
GGB, Université de Brest, Inserm, CHRU Brest, EFS, UMR 1078, F-29200 Brest, France
5
Department of Medical Biosciences, Umeå University, 90187 Umeå, Sweden
6
RECAMO, Masaryk Memorial Cancer Institute, Zluty kopec 7, 65653 Brno, Czech Republic
*
Authors to whom correspondence should be addressed.
Academic Editor: Sara N. Richter
Received: 8 November 2018 / Revised: 25 November 2018 / Accepted: 26 November 2018 / Published: 29 November 2018
(This article belongs to the Special Issue G-quadruplex and Microorganisms)
Full-Text   |   PDF [2503 KB, uploaded 29 November 2018]   |  

Abstract

Protein-RNA interactions (PRIs) control pivotal steps in RNA biogenesis, regulate multiple physiological and pathological cellular networks, and are emerging as important drug targets. However, targeting of specific protein-RNA interactions for therapeutic developments is still poorly advanced. Studies and manipulation of these interactions are technically challenging and in vitro drug screening assays are often hampered due to the complexity of RNA structures. The binding of nucleolin (NCL) to a G-quadruplex (G4) structure in the messenger RNA (mRNA) of the Epstein-Barr virus (EBV)-encoded EBNA1 has emerged as an interesting therapeutic target to interfere with immune evasion of EBV-associated cancers. Using the NCL-EBNA1 mRNA interaction as a model, we describe a quantitative proximity ligation assay (PLA)-based in cellulo approach to determine the structure activity relationship of small chemical G4 ligands. Our results show how different G4 ligands have different effects on NCL binding to G4 of the EBNA1 mRNA and highlight the importance of in-cellulo screening assays for targeting RNA structure-dependent interactions. View Full-Text
Keywords: structure-activity relationship; protein-mRNA interactions; G-quadruplexes; PhenDC3; pyridostatin; EBNA1; Epstein-Barr virus (EBV) structure-activity relationship; protein-mRNA interactions; G-quadruplexes; PhenDC3; pyridostatin; EBNA1; Epstein-Barr virus (EBV)
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Prado Martins, R.; Findakly, S.; Daskalogianni, C.; Teulade-Fichou, M.-P.; Blondel, M.; Fåhraeus, R. In Cellulo Protein-mRNA Interaction Assay to Determine the Action of G-Quadruplex-Binding Molecules. Molecules 2018, 23, 3124.

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