Elucidation of nuclear import mechanism of argonaute 2 for efficient knockdown of nuclear-localizing non-coding RNA

2015 Fiscal Year Final Research Report

• Project/Area Number: 25670013
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Physical pharmacy
• Research Institution: Osaka University
• Principal Investigator: SAKURAI FUMINORI 大阪大学, 薬学研究科(研究院), 准教授 (70370939)
• Co-Investigator(Renkei-kenkyūsha): KAMADA HARUHIKO (独)医薬基盤・健康・栄養研究所, バイオ創薬プロジェクト・サブプロジェクト, リーダー (00324509)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: Argonaute 2 / RNA干渉 / 核移行 / 細胞内動態

Outline of Final Research Achievements

In this study, we tried to elucidate nuclear import mechanism of argonaute 2 (Ago2). Several　Ago2　derivatives　containing　amino　acid　substitutions　exhibited　lower　levels　of　nuclear　accumulation, compared with wild-type Ago2. The Ago2 derivatives showing lower nuclear accumulation possessed the mutations which were important for association with protein X. We demonstrated by immunoprecipitation assay that the Ago2 derivatives showing lower nuclear accumulation exhibited low levels of association with protein X. In addition, siRNA-mediated knockdown of protein X resulted in reduction in nuclear accumulation of Ago2. These data indicate that Ago2 is imported to nucleaus by being associated with protein X.

Free Research Field

遺伝子治療学