RNA-seq of NSC-34 cells expressing SOD1

Misfolded soluble trimeric species of superoxide dismutase 1 (SOD1) are associated with increased death in neuron-like cell models and greater disease severity in amyotrophic lateral sclerosis (ALS) patients compared to insoluble protein aggregates. The mechanism by which structurally independent SOD1 trimers cause cellular toxicity is unknown but may be a driver of disease pathology. Here, we uncovered the SOD1 trimer transcriptome. We identified key pathways using transcriptomic data from motor neuron-like cells (NSC-34s) expressing SOD1 trimers. We discovered differential gene expression in cells that express SOD1 trimers with selective enrichment of genes responsible for protein localization to membranes and a global upregulation of cellular senescence pathways. Our investigation highlights key protein factors and pathways within each system, revealing a plausible intersection of genetic and pathophysiological mechanisms in ALS through interactions involving SOD1 trimers. Overall design: We cultured NSC-34 cells and transfected the cells with native SOD1 dimer or non-native SOD1 trimer. We confirmed transfection and differentiated the cells. After differentiation, we harvested the cell lysate and collected the total RNA. We then sent the samples to Novogene for library construction, sequencing, and data analysis.