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

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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.

NATURVETENSKAP Biologi Biokemi och molekylärbiologi hsv//swe
NATURAL SCIENCES Biological Sciences Biochemistry and Molecular Biology hsv//eng
structure-activity relationship
protein-mRNA interactions
G-quadruplexes
PhenDC3
pyridostatin
EBNA1
Epstein-Barr virus (EBV)

Findakly, Sarah (författare)
Daskalogianni, Chrysoula (författare)
Teulade-Fichou, Marie-Paule (författare)
Blondel, Marc (författare)
Fåhraeus, RobinUmeå universitet,Patologi,Université Paris 7, Inserm, UMR 1162, 75013 Paris, France; ICCVS, University of Gda ´nsk, Science, ul. Wita Stwosza 63, 80-308 Gda ´nsk, Poland; RECAMO, Masaryk Memorial Cancer Institute, Zluty kopec 7, 65653 Brno, Czech Republic(Swepub:umu)rofa0013 (författare)
Umeå universitetPatologi (creator_code:org_t)

Av författaren/redakt...: Martins, Rodrigo ...; Findakly, Sarah; Daskalogianni, C ...; Teulade-Fichou, ...; Blondel, Marc; Fåhraeus, Robin

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