2019 Fiscal Year Final Research Report
Molecular and cellular mechanisms underlying intercellular transfer of double stranded RNA
| Project/Area Number |
16K18517
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Functional biochemistry
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Keywords | C. elegans / RNA干渉 / systemic RNAi / 亜鉛 / 小胞輸送 |
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| Outline of Final Research Achievements |
In C. elegans, dsRNA spreads throughout the whole body and causes RNA silencing in cell non-autonomous manner. This phenomenon is termed systemic RNAi. Previous genetic studies identified several genes involved in systemic RNAi. The molecular mechanisms by which systemic spread of dsRNA occurs in C. elegans appear to be conserved, at least partly, among plants, invertebrates and vertebrates. However, molecules that mediate RNA transport between cells remain largely unknown. We previously reported that mutations in rsd-3, a gene encoding conserved ENTH domain protein, is required for efficient import of silencing RNA, and the rsd-3 mutants displayed an incomplete defect in systemic RNAi. From a genetic screen for mutations able to suppress the defective RNAi phenotype of rsd-3 mutants, we found a zinc transporter gene is the causal gene of the suppression phenotype.
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| Free Research Field |
分子遺伝学
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| Academic Significance and Societal Importance of the Research Achievements |
細胞間を伝播するという「可動性」と遺伝子配列に応じた作用するという「特異性」と「汎用性」から機能性RNAを使った遺伝子治療は魅力的なアプローチの一つである。最近になり一部の核酸医薬品が実用化されているが、未だに一回あたりの投与量が多く、治療費が高額になるという問題もある。このように、未だに十分な送達システムが構築されたとは言えない状況である。本研究で新たに亜鉛の膜輸送を介した小胞輸送が機能性RNAの細胞間の移動に関与することが明らかになった。この発見を創薬研究に発展させることで、近い将来核酸医薬品などの送達システムの開発に貢献することになると期待できる。
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