2010 Fiscal Year Final Research Report
Research on the pathophysiology and treatment of neurological disorders modified by nonsense-mediated mRNA decay (NMD)
| Project/Area Number |
20591015
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | National Institute for Minamata Disease |
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Principal Investigator |
USUKI Fusako National Institute for Minamata Disease, 臨床部, 室長 (50185013)
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| Co-Investigator(Kenkyū-buntansha) |
山下 暁朗 横浜市立大学, 医学部・微生物学, 講師 (20405020)
樋口 逸郎 鹿児島大学, 医学部・老年神経内科, 准教授 (80183573)
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| Project Period (FY) |
2008 – 2010
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| Keywords | Nonsense-mediated mRNA decay (NMD) / NMD構成分子 / siRNA, NMD抑制 / Ullrich病繊維芽細胞 / 腫瘍細胞 / 細胞生理機能 / 生体ストレス応答 |
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| Research Abstract |
Nonsense-mediated mRNA decay (NMD), an mRNA quality surveillance mechanism, affects disease condition by modifying post-transcriptionally the expression of disease-related gene carrying premature termination codons (PTCs). Among them some disease conditions are recovered by NMD suppression, which up-regulates the mutant mRNA and restores partially the defect of protein and cellular function. Using Ullrich's disease fibroblasts as a model cell line of PTC-harbored genetic diseases exacerbated by NMD, we investigated effects of NMD suppression on cellular physiological functions. NMD suppression by siRNAs targeted to NMD components neither affects cellular cycle nor causes ER stress. However, knockdown of 6 NMD components except SMG-8 suppressed cell growth although the effects were much milder than those on epithelial carcinoma cell line (HeLa cells). In addition, we clarified that selenoenzymes were affected by NMD execution and oxidative stress was induced under selenium deficiency by exposure to a chemical toxin.
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