| 研究課題/領域番号 |
18F18098
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| 研究機関 | 国立感染症研究所 |
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研究代表者 |
アリ フセインハッサン 国立感染症研究所, ウイルス第二部, 主任研究官 (00523515)
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| 研究分担者 |
IBRAHIM MARWA 国立感染症研究所, ウイルス第二部, 外国人特別研究員
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| 研究期間 (年度) |
2018-10-12 – 2021-03-31
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| キーワード | HBV / RNA degradation / MafF / IL-1b / HBV-pgRNA |
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| 研究実績の概要 |
We previously showed that the inflammatory cytokine IL-1b induced HBV-RNA degradation through the induction of Ski2 (an important adaptor of RNA-exosome, and RNA degradation). Interestingly Marwa showed that IL-1b suppressed HBV-pgRNA levels, and that this suppression was regulated by MafF. We found MafF binding site on HBV-core promoter where MafF acted as a transcriptional repressor. However, mutations in this MafF binding site, blocking MafF/HBV-core promoter interaction, partially (1/3) rescued HBV-pgRNA levels. These data suggested another mechanism by which MafF suppress HBV-pgRNA. Northern blot analysis showed that MafF induced HBV-pgRNA degradation. Marwa is recently analyzing the mechanism of RNA decay affected by MafF.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
Marwa identified two different mechanisms by which MafF suppress HBV replication. She showd that MafF directly interact and suppress transcription from HBV-core promoter. She also showed that MafF suppress HBV-pgRNA levels through the induction of its degradation. From now on, she will focus on analyzing the mechanism by which MafF induce this degradation.
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| 今後の研究の推進方策 |
From now on, she will focus on analyzing the mechanism by which MafF induce this degradation. Loss of function of key factor s (EXOSC3, HBS1L, Ski2, XRN1,...) will be performed, and its effect on MafF regulation of HBV-pgRNA decay will be analyzed.The effect of MafF on the expression of the identified factors will be quantified. The mechanism by which MafF affect the expression of these genes, and its regulation by anti-viral cytokines will be further investigated. Data will be drafted into a paper and submitted.
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