• Top page
  • Timetable
  • Per session
  • Per presentation
  • How to
  • Meeting Planner

演題詳細

Symposium

神経発生と疾患におけるRNA制御機構
RNA regulation in neural development and diseases

開催日 2014/9/11
時間 14:00 - 16:00
会場 Room E(301)
Chairperson(s) 河原 行郎 / Yukio Kawahara (大阪大学大学院医学系研究科遺伝子機能制御学 / Osaka University, Graduate School of Medicine, Japan)
築地 仁美 / Hitomi Tsuiji (名古屋市立大学大学院薬学研究科 病態生化学分野 / Department of Biomedical Science, Nagoya City University, Graduate School Pharmaceutical Science, Japan)

神経変性疾患関連蛋白質Ataxin-2によるRNA代謝制御の全体像
Elucidation of Ataxin-2-mediated regulation of RNA metabolism

  • S1-E-2-3
  • 河原 行郎 / Yukio Kawahara:1 
  • 1:大阪大学 / Osaka University, Graduate School of Medicine, Japan 

Spinocerebellar ataxia type 2 is an autosomal dominant neurodegenerative disease. The disorder is caused by abnormal CAG repeat expansion in the coding region of the Ataxin-2 gene (ATXN2). Recently, moderate CAG repeat expansion in ATXN2 was identified as a risk factor for amyotrophic lateral sclerosis. This finding suggests a common pathogenic role of Ataxin-2 in these neurodegenerative diseases. It has been proposed that Ataxin-2, a member of the LSm protein family, participates in the regulation of RNA metabolism through interaction with PABPC1. However, the exact biological mechanism and in vivo targets remain unknown. Here we report that Ataxin-2 binds directly to RNAs in a PABPC1-independent manner. High-throughput sequencing of Ataxin-2-bound RNAs prepared by PAR-CLIP revealed that Ataxin-2 binds predominantly to uridine-rich elements, including well-characterized cis-regulatory AU-rich elements, in the 3'UTRs of target mRNAs. Gene expression analysis after Ataxin-2 depletion or overexpression revealed that Ataxin-2 stabilizes target mRNAs and increases the abundance of the corresponding proteins. A tethering assay demonstrated that Ataxin-2 elicits this effect by direct interaction with mRNAs. We also found that disease-associated polyglutamine expansion downregulates the physiological activity of Ataxin-2. These findings suggest that Ataxin-2 is an RNA-binding protein that targets cis-regulatory elements in 3'UTRs to stabilize a subset of mRNAs and increase protein expression.

Copyright © Neuroscience2014. All Right Reserved.