Investigation of protein-RNA interaction implicated in neurodegeneration

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09822
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: University of Tsukuba
• Principal Investigator: Higashi Shinji 筑波大学, 医学医療系, 講師 (30365647)
• Research Collaborator: ARAI Tetsuaki 筑波大学, 医学医療系, 教授 (90291145) ; AKIYAMA Haruhiko 公益財団法人東京都医学総合研究所, 認知症・高次脳機能研究分野, 研究員 (20231839) ; ISEKI Eizo 順天堂大学, 医学部 (30203061)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 筋萎縮性側索硬化症 / 前頭側頭葉変性症 / TDP-43 / RNA metabolism / 凝集体 / 神経変性

Outline of Final Research Achievements

We investigated the effect of truncation of TDP-43 on the expression of poly(A)+ RNA by fluorescence in situ hybridization using HeLa cells transfected with a series of deleted TDP-43 constructs. Endogenous and overexpressed full-length TDP-43 localized to the perichromatin region and interchromatin space adjacent to poly(A)+ RNA. Deleted variants of TDP-43 containing RNA recognition motif 1 and truncating N-terminal region induced cytoplasmic inclusions in which poly(A)+ RNA was recruited. C-terminal TDP-43 truncated at residue 202 or 218 was distributed in the cytoplasm as punctate structures. C-terminal TDP-43 truncated at residue 218 but not at 202 significantly decreased poly(A)+ RNA expression by approximately 24% compared with the level in control cells. Thus, a disturbance of the RNA metabolism in which TDP-43 is involved may be central to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD).

Free Research Field

神経変性疾患