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| Status |
Public on Feb 01, 2018 |
| Title |
MiR-129-5p downregulates HuD expression impairing neuritogenesis in Amyotrophic Lateral Sclerosis |
| Organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by high throughput sequencing
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| Summary |
Amyotrophic 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 and HuD as key regulators of neuronal differentiation and as potential therapeutic targets for ALS.
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| Overall design |
Human neuroblastoma SHSY-5Y cells stably transfected with cDNAs coding for wild type SOD1, four biological replicates, or the mutant SOD1(G93A), four biological replicates, were sequenced
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| Contributor(s) |
Loffreda A, Arosio A, Ruepp M, Calogero RA, Volinia S, Bendotti C, Ferrarese C, Lunetta C, Mühlemann O, Tremolizzo L, Barabino SM |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Feb 01, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Raffaele A Calogero |
| E-mail(s) |
raffaele.calogero@unito.it
|
| Phone |
++39 0116706454
|
| Organization name |
University of Torino
|
| Department |
Molecular Biotechnology Center
|
| Lab |
Bioinformatics and Genomics Unit
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| Street address |
Via Nizza 52
|
| City |
Torino |
| State/province |
To |
| ZIP/Postal code |
10126 |
| Country |
Italy |
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| Platforms (1) |
| GPL13393 |
AB SOLiD 4 System (Homo sapiens) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA369538 |
| SRA |
SRP098698 |
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