RNA epigenetics regulation by ABH family and regulation failure mechanism in cancer
| Project/Area Number |
26293015
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2016: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2014: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
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| Keywords | RNAエピジェネティクス / ABHファミリー / ALKBH / 癌 / エピジェネティクス / がん / RNA / 脱メチル化 / 薬学 |
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| Outline of Final Research Achievements |
AlkB homolog 3 (ABH3, ALKBH3), which is originally designated as prostate cancer antigen-1, is highly expressed in prostate cancer, pancreatic cancer, and non-small-cell lung cancer. ALKBH3 catalyzes the demethylation of 1-methyladenine (1-meA), 3-methylcytosine (3-meC), and N6-methyladenine (N6-meA) in DNA and RNA. In this study, ALKBH3 was found to effectively demethylate 1-meA, 3-meC, and N6-meA within endogenously methylated RNA. An in vitro translation assay showed that ALKBH3-demethylated tRNA significantly enhanced protein translation efficiency. In addition, ALKBH3 knockdown in Panc-1 cells suppressed the nascent protein synthesis. Thus, our data highlight a novel role for ALKBH3 in tumor progression via RNA demethylation and subsequent protein synthesis promotion. Moreover, ALKBH family molecules were found to demethylate specific methylated bases in RNA. These results open a new avenue for RNA epigenetic regulation by ALKBH family molecules.
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Report
(4 results)
Research Products
(19 results)
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[Presentation] ABH3のRNA脱メチル化を介したタンパク質翻訳制御機構の解明2015
Author(s)
河口恵, 上田裕子, 北惠郁緒里, 仲井秀一, 大塩郁幹, 小林巧明, 神宮司健太郎, 深田宗一朗, 青木俊二, 馬淵美雪, 田中明人, 辻川和丈
Organizer
日本薬学会第135年会
Place of Presentation
兵庫医療大学（神戸）
Year and Date
2015-03-27
Related Report
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