| Budget Amount *help |
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2014: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2013: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2012: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
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| Outline of Final Research Achievements |
Spinocerebellar ataxia type 10 (SCA10) is a dominantly inherited neurodegenerative
disorder caused by unstable expansion of ATTCT repeats in intron 9 of ATXN10 gene on chromosome 22q13.31. The mechanism by which the ATTCT expansion causes the SCA10 phenotype is still unknown. Here we present data suggesting that expanded AUUCU RNA triggers neuronal dysfunctions. We detected intranuclear AUUCU inclusions in SCA10 cells by RNA-FISH, similar to other non-coding repeat expansion disorders. Furthermore, we characterized their intranuclear localization and nucleic acid contents, demonstrating that the inclusions are located at perinucleolar compartments and enriched for the AUUCU expansion, but not intronic flanking sequences. Several RNA-binding proteins were found to bind AUUCU repeats, including splicing factor PTBP1, which regulates neuronal-specific PTBP2 splicing during neurodevelopment. SCA10 cells showed aberrant splicing of PTBP2 and significantly increased PTBP2 protein levels.
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