Arginine methylation-mediated regulation on the nucleo-cytoplasmic shuttling and the aggregates of FUS/TLS

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461267
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Chiba University
• Principal Investigator: Yamaguchi Atsushi 千葉大学, 医学(系)研究科(研究院), 准教授 (00314336)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: ALS

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.

Free Research Field

神経生物学