| Project/Area Number |
15K06827
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Kazumi Nakano 東京大学, 大学院新領域創成科学研究科, 准教授 (60549591)
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| Co-Investigator(Kenkyū-buntansha) |
渡邉 俊樹 聖マリアンナ医科大学, 医学研究科, 教授 (30182934)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | HTLV-1 / ウイルスタンパク質 / RNA輸送 / NMD / Rex / インテラクトーム / 遺伝子発現 / mRNA / スプライシング / 翻訳 / 発がんウイルス / ATL / ＨＴＬＶ－１ / ＡＴＬ / ウイルス発癌 / ＲＮＡ核外輸送 / 宿主ウイルス相互作用 / ウイルスRNA / RNA代謝 / ウイルス発がん |
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| Outline of Final Research Achievements |
Human T-cell leukemia virus type-I (HTLV-1) is responsible for development of adult T- cell leukemia (ATL). HTLV-1 encodes a viral RNA binding protein, Rex, which regulates the quantity and timing of viral replication through viral mRNA-specific nuclear-export and protection by inhibition of cellular nonsense mediated mRNA decay (NMD). Here we show a possibility that during the formation of UPF1-UPF2-UPF3B complex in the onset of NMD pathway, Rex may replace UPF3B with UPF3A to suppress the normal NMD activity. Also we demonstrate that Rex interacts with at least 81 human cellular proteins, which are enrolled in transcription, splicing, mRNA metabolism, and translation. These data propose a possibility that Rex may invade into these pathways to adjust the cellular environment beneficial for the viral replication. On the other hand, these unexpected functions of Rex may increase the risk of dysregulation in the function and homeostasis of the host cell.
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