Research on environmental stresses-induced change in nonsense-mediated mRNA decay (NMD) activity and its effect on pathological conditions

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460402
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: National Institute for Minamata Disease
• Principal Investigator: Usuki Fusako 国立水俣病総合研究センター, その他部局等, 部長 (50185013)
• Co-Investigator(Kenkyū-buntansha): FUJIMURA Masatake 国立水俣病総合研究センター, 基礎研究部, 室長 (20416564)
• Co-Investigator(Renkei-kenkyūsha): YAMASHITA Akio 横浜市立大学医学部, 分子細胞生物学, 准教授 (20405020)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 環境ストレス / mRNA監視機構(NMD) / eIF2αリン酸化 / NMD抑制 / 早期終止コドン(PTC) / 蛋白質翻訳抑制 / Snhg1 mRNA

Outline of Final Research Achievements

Nonsense-mediated mRNA decay (NMD), an mRNA quality surveillance mechanism, was suppressed under environmental stresses and mild endoplasmic reticulum (ER) stress preconditioning. NMD suppression under mild ER stress preconditioning up-regulated the expression of mutant disease-related mRNA carrying premature termination codon (PTC) and restored partially the defect of protein. Mild ER stress preconditioning-induced NMD suppression was caused by phospho-eukaryotic initiation factor 2α- mediated translation suppression and downregulation of some NMD components. Environmental stresses and ER stress preconditioning has potential to affect phenotypes of PTC-related diseases.

Free Research Field

分子病態医化学