Functional assessment of FRDA-3′-UTR versus WT-3′-UTR.

<p> U2OS (black bars) and HEK-293 (grey bars) cells were transfected with luciferase reporter gene system, respectively 150 ng of empty plasmid or plasmid WT-3′-UTR or plasmid FRDA-3′-UTR. Histograms show the <i>Renilla</i> luciferase activity (normalized to firefly luciferase and to the mock transfected cells) following transfection of each plasmid into both cell lines. All results represent mean ± SEM of three independent experiments, each in triplicate. *<i>P</i><0.05, Student-t test.</p

Genotype frequencies of the five SNPs for the <i>FXN</i> 3′-UTR in cases, cases from the replication study (RS-cases), and controls.

<p>Genotype frequencies of the five SNPs for the <i>FXN</i> 3′-UTR in cases, cases from the replication study (RS-cases), and controls.</p

Distribution of the most common haplotypes.

<p>Genotype frequencies of haplotypes in cases, controls and the replication study cases (RS-cases) are plotted as pie charts for the most common haplotypes of the <i>FXN</i> 3′-UTR (TGCTT, CATCG, CATCT). Haplotype TATTT was uniquely found among RS-cases.</p

Genetic association of ITR3 and SNPs of the <i>FXN</i> 3′-UTR with FRDA haplotype in cases versus controls.

<p>Genetic association of ITR3 and SNPs of the <i>FXN</i> 3′-UTR with FRDA haplotype in cases versus controls.</p

Computational analysis of miRNA targeting on <i>FXN</i> 3′-UTR.

<p>Computational analysis of miRNA targeting on <i>FXN</i> 3′-UTR.</p

Schematized representation of the genomic structure of the <i>FXN</i> gene.

<p> The pathogenic expansion of the GAA repeat within intron 1 is indicated by a triangle, exons by grey boxes, respectively dark when translated and light when untranslated. Short genetic variations are indicated as black bars. The <i>FXN</i> 3′-UTR region, which was sequenced is highlighted by a square bracket.</p

Frequencies of the haplotypes comprising the five SNPs of the <i>FXN</i> 3′-UTR.

<p>Frequencies of the haplotypes comprising the five SNPs of the <i>FXN</i> 3′-UTR.</p

RNA-binding proteins are a major target of silica nanoparticles in cell extracts

<p>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 <i>in vitro</i> assay, we showed that the sequestration of translation initiation factors by silica NPs results in an inhibition of the <i>in vitro</i> translational activity. This result demonstrates that characterizing the protein corona of various NPs would be a relevant approach to predict their potential toxicological effects.</p