2018 Fiscal Year Final Research Report
Creation of RNA aptamers aiming at the creation of new antifungal drug
| Project/Area Number |
16K14652
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Medical genome science
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| Research Institution | Kindai University |
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Principal Investigator |
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| Research Collaborator |
YAMASAKI manabu
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | RNAアプタマー |
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| Outline of Final Research Achievements |
Using the fungal capping enzymes Ceg1, Cet1 and Cet1 mutants that can not bind to Ceg1, we show that nuclear translocation signals are present only in Cet1, and that Ceg1 can not translocate to the nucleus without binding to Cet1. Furthermore, we demonstrate that Cet1 and Ceg1 bind in the cytoplasm, and that the Cet1-Ceg1 complex translocates to the nucleus. Moreover, genetic studies using yeast show that Cet1 and Ceg1 binding is essential for fungal growth. These data indicate that inhibition of Cet1-Ceg1 binding may be the mechanism of action of novel antifungal agents. Then, we obtained the aptamers that selectively inhibit the capping reaction of budding yeast that has been used as a model so far.
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| Free Research Field |
RNA生化学
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| Academic Significance and Societal Importance of the Research Achievements |
真菌と哺乳類とで異なる反応経路をとるmRNAのcapping反応に着目し、真菌のcapping反応のみを阻害するRNAアプタマーの創製を試みた。その結果、Cet1-Ceg1結合阻害が新規抗真菌薬の作用機序となりうる事が示し、これまでにモデルとした出芽酵母のcapping反応を選択的に阻害するアプタマーを取得している。また、今後作動性が確認されたRNAアプタマーはそれ自身を修飾すること、またはその構造を解析することによる新規化合物のスクリーニングにより、抗真菌薬開発に応用可能である。
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