| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Outline of Final Research Achievements |
FUS/TLS (Fused in Sarcoma/Translocated in liposarcoma) encodes a multifunctional DNA/RNA binding protein with non-classical carboxy (C)-terminal nuclear localization signal (NLS). A variety of ALS-linked mutations are clustered in the C-terminal NLS, resulting in the cytoplasmic mislocalization and aggregation. We here examined effects of methylation on the cytoplasmic mislocalization and aggregates of FUS mutant in a cell culture system. We also examined the effects of FUS-derived aggregates on ALS-associated RNA binding proteins and RNA granules. Treatment with global methyltransferase inhibitor remarkably mitigated the cytoplasmic mislocalization and aggregation of FUS mutant. In addition, the aggregates of FUS C-terminal mutants sequestered hnRNP A1, hnRNP A2, and SMN1 as well as FUS wild type into the FUS mutant-derived spontaneous aggregates in the cytoplasm.
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