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 |
Research Field |
Neurology
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Research Institution | Niigata University |
Principal Investigator |
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Project Period (FY) |
2013-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | 筋萎縮性側索硬化症 / 神経病態 / RNA代謝 / RNA結合蛋白 |
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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Report
(4 results)
Research Products
(13 results)
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[Journal Article] C9ORF72 repeat-associated non-ATG-translated polypeptides are distributed independently of TDP-43 in a Japanese patient with c9ALS.2014
Author(s)
Konno T, Tada M, Shiga A, Tsujino A, Eguchi H, Masuda-Suzukake M, Hasegawa M, Nishizawa M, Onodera O, Kakita A, Takahashi H.
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Journal Title
Neuropathol Appl Neurobiol.
Volume: 40
Pages: 783-788
DOI
Related Report
Peer Reviewed
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[Journal Article] Japanese amyotrophic lateral sclerosis patients with GGGGCC hexanucleotide repeat expansion in C9ORF72.2013
Author(s)
Konno T, Shiga A, Tsujino A, Sugai A, Kato T, Kanai K, Yokoseki A, Eguchi H, Kuwabara S, Nishizawa M, Takahashi H, Onodera O.
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Journal Title
J Neurol Neurosurg Psychiatry.
Volume: 84
Pages: 398-401
DOI
Related Report
Peer Reviewed
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