2016 Fiscal Year Final Research Report
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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| Keywords | RNAエピジェネティクス / ABHファミリー / ALKBH / 癌 |
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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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| Free Research Field |
生物系薬学
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