GSE87495 DUX4-induced dsRNA and MYC mRNA Stabilization Lead to Apoptosis in Human Cell Models of Facioscapulohumeral Dystrophy

Contributors : Sean C Shadle ; Jun W Zhong ; Amy E Campbell ; Melissa L Conerly ; Sujatha Jagannathan ; Chao-Jen Wong ; Timothy D Morello ; Stephen J TapscottSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensFacioscapulohumeral muscular dystophy (FSHD) is caused by the mis-expression of DUX4 in skeletal muscle cells. DUX4 is a transcription factor that activates genes normally associated with stem cell biology and its mis-expression in FSHD cells results in apoptosis. To identify genes and pathways necessary for DUX4-mediated apoptosis, we performed an siRNA screen in an RD rhabdomyosarcoma cell line with an inducible DUX4 transgene. Our screen identified components of the MYC-mediated apoptotic pathway and the double-stranded RNA (dsRNA) innate immune response pathway as mediators of DUX4-induced apoptosis. Further investigation revealed that DUX4 expression led to stabilization and accumulation of MYC mRNA, as well as an accumulation of dsRNA and activation of the dsRNA response pathway in both RD cells and human myoblasts. These findings demonstrate that RNA stabilization and the accumulation of MYC mRNA and dsRNA are a major cause DUX4 toxicity in human cells.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research