| Budget Amount *help |
¥25,350,000 (Direct Cost: ¥19,500,000、Indirect Cost: ¥5,850,000)
Fiscal Year 2019: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2018: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2017: ¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000)
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| Outline of Final Research Achievements |
An intronic GGGGCC (G4C2) repeat expansion in C9orf72 gene was identified as a leading genetic cause of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). The hexanucleotide DNA repeat is bidirectionally transcribed into repeat RNA accumulating within RNA foci. We revealed the repeat RNA is even translated into five distinct proteins called dipeptide-repeat protein (DPR)s in the absence of the canonical translation initiation codon (AUG). Since the identification of DPR, cytotoxic properties of DPR has been extensively shown in multiple disease models. In the current study, we identified a factor directly involved in the metabolism of the repeat RNA. Moreover, pathogenic DPR inhibits the enzymatic activity of the factor.
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