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 mRNA profiles of NSC34 PR20-resistant clones and untreated cells were generated by deep sequencing. Differential gene expression pathway analyses were performed.