The protective role of RNA chaperone for RNA misfolding in neurodegeneraiton

2015 Fiscal Year Final Research Report

• Project/Area Number: 15K15334
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: ISHIGURO TARO 東京医科歯科大学, 医歯学総合研究科, 助教 (20748587)
• Project Period (FY): 2015-04-01 – 2016-03-31
• Keywords: SCA31 / RNA foci / RNAシャペロン / RNAミスフォールディング / マイクロサテライトリピート病 / RNA結合タンパク質 / ショウジョウバエ

Outline of Final Research Achievements

Microsatellite expansion disorders are pathologically characterized by RNA foci formation. We report that expression of expanded UGGAA (UGGAAexp) repeats, responsible for spinocerebellar ataxia type 31 (SCA31) in Drosophila, causes neurodegeneration accompanied with accumulation of UGGAAexp RNA foci, consistent with observations in SCA31 patient brains. We identified the several RNA-binding proteins (RBP), which binds to UGGAAexp and induces structural alteration of UGGAAexp. Furthermore, co-expression of the mutant with RNA-recognition motif mutation failed to rescue UGGAAexp-mediated degeneration. These data sugesst that the RBP suppresses UGGAAexp-mediated neurotoxicity in Drosophila to function as RNA chaperones for proper UGGAAexp folding and regulation by direct binding to UGGAA repeat RNA.

Free Research Field

脳神経科学・神経内科学