Analysis of molecular mechanism underlying ADAR2 down-regulation in ALS motor neurons

2016 Fiscal Year Final Research Report

• Project/Area Number: 25253063
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: The University of Tokyo
• Principal Investigator: Kwak Shin 東京大学, 大学院医学系研究科(医学部), 客員研究員 (40160981)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: ALS / RNA編集 / ADAR2遺伝子 / 転写因子 / FUS

Outline of Final Research Achievements

Amyotrophic lateral sclerosis (ALS) is the most common and fatal adult-onset motor neuron disease. Deficient RNA editing resulting from down-regulation of RNA editing enzyme called adenosine deaminase acting on RNA 2 (ADAR2) is closely relevant pathogenic abnormality to sporadic ALS that accounts for more than 90% of ALS patients. Because how ADAR2 gene expression is regulated is not known, we investigated the transcription factors (TFs) that specifically regulate the ADAR2 gene expression in the human motor neurons in order to elucidate the mechanism underlying ADAR2 down-regulation in ALS.
We dissected specific motor neuron tissue by laser-capture microdissection and conducted cap analysis of gene expression (CAGE) on the extracted RNA. We surveyed the TFs binding motifs in the regions expressing CAGE tags in the promoter regions of the ADAR2 gene. Several of the resulting TFs exhibited regulatory activity on the ADAR2 gene by luciferase reporter assay for the ADAR2 gene promoter.

Free Research Field

神経内科