title: RNA-binding proteins are a major target of silica nanoparticles in cell extracts.
abstract: Upon contact with biological fluids, nanoparticles (NPs) are readily coated by cellular compounds, particularly proteins, which are determining factors for the localization and toxicity of NPs in the organism. Here, we improved a methodological approach to identify proteins that adsorb on silica NPs with high affinity. Using large-scale proteomics and mixtures of soluble proteins prepared either from yeast cells or from alveolar human cells, we observed that proteins with large unstructured region(s) are more prone to bind on silica NPs. These disordered regions provide flexibility to proteins, a property that promotes their adsorption. The statistical analyses also pointed to a marked overrepresentation of RNA-binding proteins (RBPs) and of translation initiation factors among the adsorbed proteins. We propose that silica surfaces, which are mainly composed of Si-O-and Si-OH groups, mimic ribose-phosphate molecules (rich in -O-and -OH) and trap the proteins able to interact with ribose-phosphate containing molecules. Finally, using an in vitro assay, we showed that the sequestration of translation initiation factors by silica NPs results in an inhibition of the in vitro translational activity. This result demonstrates that characterizing the protein corona of various NPs would be a relevant approach to predict their potential toxicological effects.
authors.affiliation: a I2BC, IBITEC-S, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay , Gif-sur-Yvette , France.|b LIONS, NIMBE, CEA, CNRS, Université Paris-Saclay, CEA Saclay , Gif-sur-Yvette , France.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Klein
authors.affiliation: a I2BC, IBITEC-S, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay , Gif-sur-Yvette , France.|b LIONS, NIMBE, CEA, CNRS, Université Paris-Saclay, CEA Saclay , Gif-sur-Yvette , France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Mathé
authors.affiliation: c Univ. Grenoble Alpes, CEA, INAC-SyMMES, Laboratoire Lésions des Acides Nucléiques , Grenoble , France , and.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Biola-Clier
authors.affiliation: b LIONS, NIMBE, CEA, CNRS, Université Paris-Saclay, CEA Saclay , Gif-sur-Yvette , France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Devineau
authors.affiliation: a I2BC, IBITEC-S, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay , Gif-sur-Yvette , France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Drouineau
authors.affiliation: a I2BC, IBITEC-S, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay , Gif-sur-Yvette , France.
authors.forename: Elie
authors.initials: E
authors.lastname: Hatem
authors.affiliation: a I2BC, IBITEC-S, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay , Gif-sur-Yvette , France.|b LIONS, NIMBE, CEA, CNRS, Université Paris-Saclay, CEA Saclay , Gif-sur-Yvette , France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Marichal
authors.affiliation: d CEA-Marcoule, DRF/IBITEC-S/SPI/Li2D, Laboratory 'Innovative technologies for Detection and Diagnostics', BP 17171 , Bagnols-sur-Cèze , France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Alonso
authors.affiliation: d CEA-Marcoule, DRF/IBITEC-S/SPI/Li2D, Laboratory 'Innovative technologies for Detection and Diagnostics', BP 17171 , Bagnols-sur-Cèze , France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Gaillard
authors.affiliation: a I2BC, IBITEC-S, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay , Gif-sur-Yvette , France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Lagniel
authors.affiliation: d CEA-Marcoule, DRF/IBITEC-S/SPI/Li2D, Laboratory 'Innovative technologies for Detection and Diagnostics', BP 17171 , Bagnols-sur-Cèze , France.
authors.forename: Jean
authors.initials: J
authors.lastname: Armengaud
authors.affiliation: c Univ. Grenoble Alpes, CEA, INAC-SyMMES, Laboratoire Lésions des Acides Nucléiques , Grenoble , France , and.
authors.forename: Marie
authors.initials: M
authors.lastname: Carrière
authors.affiliation: a I2BC, IBITEC-S, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay , Gif-sur-Yvette , France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Chédin
authors.affiliation: a I2BC, IBITEC-S, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay , Gif-sur-Yvette , France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Boulard
authors.affiliation: b LIONS, NIMBE, CEA, CNRS, Université Paris-Saclay, CEA Saclay , Gif-sur-Yvette , France.
authors.forename: Serge
authors.initials: S
authors.lastname: Pin
authors.affiliation: b LIONS, NIMBE, CEA, CNRS, Université Paris-Saclay, CEA Saclay , Gif-sur-Yvette , France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Renault
authors.affiliation: a I2BC, IBITEC-S, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay , Gif-sur-Yvette , France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Aude
authors.affiliation: a I2BC, IBITEC-S, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay , Gif-sur-Yvette , France.
authors.forename: Jean
authors.initials: J
authors.lastname: Labarre
mesh_terms: D000072283:A549 Cells; D000327:Adsorption; D002457:Cell Extracts / Q000737:chemistry*; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D010316:Particle Size; D010442:Peptide Chain Initiation, Translational; D011487:Protein Conformation; D040901:Proteomics; D012331:RNA, Fungal / Q000737:chemistry; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000648:ultrastructure; D012822:Silicon Dioxide / Q000737:chemistry / Q000633:toxicity*; D013499:Surface Properties
chemical_list: D002457:Cell Extracts; D012331:RNA, Fungal; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D012822:Silicon Dioxide
keywords: Protein corona; RNA binding protein; intrinsically disordered protein; proteomics; silica nanoparticles