GSE94379 MiR-129-5p downregulates HuD expression impairing neuritogenesis in Amyotrophic Lateral Sclerosis

Contributors : Alessia Loffreda ; Alessandro Arosio ; Marc-David Ruepp ; Raffaele A Calogero ; Stefano Volinia ; Caterina Bendotti ; Carlo Ferrarese ; Christian Lunetta ; Oliver M ühlemann ; Lucio Tremolizzo ; Silvia M BarabinoSeries Type : Non-coding RNA profiling by high throughput sequencingOrganism : Homo sapiensAmyotrophic lateral sclerosis (ALS) involves the degeneration of brain and spinal cord motor neurons. Mutations in Superoxide Dismutase 1 (SOD1), TAR DNA-binding protein 43 (TDP-43) and Fused-in-Sarcoma (FUS) account for 20-30 % of the familial ALS (fALS) cases. The RNA-binding proteins TDP-43 and FUS function in mRNA and miRNA biogenesis. MiRNAs are required for survival of neurons and deregulation of miRNA expression has been reported in several neurodegenerative disorders. Here, we report the dysregulation of DROSHA, DGCR8, and DICER in human neuroblastoma SH-SY5Y cells expressing the ALS-associated SOD1(G93A) mutant protein. MiRNA profiling in SH-SY5Y/SOD1(G93A) cells and transgenic SOD1(G93A) mice revealed upregulation of miR-129-5p at the early stage of disease. Moreover, miR-129-5p is also upregulated in lymphocytes of sporadic ALS patients. We demonstrate that miR-129-5p targets ELAVL4/HuD mRNA by binding to its 3 ’ UTR, which reduces HuD expression and impairs differentiation and neurite outgrowth. Conversely, treatment with an antagomir or complementation with HuD protein restores neuritogenesis. Collectively, our study identifies miR-129-5p ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Non-coding RNA profiling by high throughput sequencing Homo sapiens Source Type: research