A chemical screen identifies compounds limiting the toxicity of C9ORF72 dipeptide repeats

Purpose: Compare parental NSC34 cells with NSC34 PR20-resistant clones Methods: NSC-34 cell cultures were treated with PR20, a peptide that contains 20 copies of Proline-Arginine aminoacids, for two weeks. mRNA profiles of resistant clones were generated by RNAseq. Sequencing reads were aligned and analyzed for differential gene expression. Results: NSC34 clones that gained spontaneous resistance to PR20 present a higher levels of translation than parental cells. Gene Set Enrichment Analysis (GSEA) of this dataset revealed an overall upregulation of factors from the “mTORC1 signaling” hallmark Overall design: mRNA profiles of NSC34 PR20-resistant clones and untreated cells were generated by deep sequencing. Differential gene expression pathway analyses were performed.