2015 Fiscal Year Final Research Report
Identification of splicing factors that bind to expanded GGGGCC repeat and TDP-43 mRNA
| Project/Area Number |
25670417
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Neurology
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| Research Institution | Niigata University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | 筋萎縮性側索硬化症 |
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| Outline of Final Research Achievements |
Expansion of a GGGGCC (G4C2) repeat in the first intron of C9ORF72 is the most common cause of familial frontotemporal lobar degeneration and amyotrophic lateral sclerosis (FTLD/ALS). TAR DNA-binding protein 43 (TDP-43), encoded by TARDBP, is a major component of neuronal cytoplasmic inclusions, which are observed in affected neurons in patients with ALS. TDP-43 pathology is also observed in patients with the G4C2 repeat expansion. We have hypothesized that the repeat expansion might cause dysregulation of the alternative splicing of TDP-43 mRNA. We generated (G4C2)9 repeats as a normal control or (G4C2)82 repeats expression vectors and identified binding proteins. We transfected these RBPs siRNA into HEK293T cells and analyzed the TDP-43 alternative splicing. We performed in-situ hybridization and immunofluorescent double staining analysis using HEK293T cells. We found two G4C2 binding RBPs. However, we could not observe these proteins co-localized with (G4C2)82 repeats foci.
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| Free Research Field |
神経内科学
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