| Project/Area Number |
16H04745
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Molecular biology
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| Research Institution | Kindai University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
三嶋 雄一郎 京都産業大学, 総合生命科学部, 准教授 (00557069)
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| Research Collaborator |
ADACHI shungo
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2018: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2017: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2016: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
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| Keywords | 翻訳制御 / mRNP / mRNA分解 / mRNA分解制御 / RNAタンパク質複合体（RNP） / RNA分解制御 / mRNA-タンパク質複合体（mRNP） / RNA結合タンパク質 / mRNAメタ情報 / RNA生化学 |
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| Outline of Final Research Achievements |
We show that ZFP36L1 represses translation initiation, and demonstrate that this effect is independent of deadenylation mediated by the ARE. Strikingly, ZFP36L1-mediated translation repression nevertheless requires interaction between ZFP36L1 and CNOT1. Moreover, the eIF4F complex remains bound to the mRNA even in the presence of ZFP36L1. These observations imply that ZFP36L1-mediated repression of translation initiation differs fundamentally from the mechanism used by miRISC. Moreover, we find that translational repression by ZFP36L1 is also independent of 4EHP, despite this being a key factor for translation repression by ZFP36L. Collectively, our results highlight surprising diversity of regulatory mechanisms used by ARE-BPs and factors that interact with the CCR4/NOT co-factor complex.
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| Academic Significance and Societal Importance of the Research Achievements |
AREは炎症性サイトカインmRNAの3'非翻訳領域に存在し、mRNAの運命決定およびタンパク質合成量を厳密に制御する。これまでの知見では、AREはRNA結合タンパク質に認識され、多くの場合脱アデニル化複合体を介したpolyA鎖の分解を基点にmRNA分解が誘導される。一方、これらARE結合タンパク質による翻訳制御機構に関する知見はこれまで乏しかった。本研究課題の遂行により、ARE結合タンパク質による翻訳抑制はpolyA鎖の分解とは独立に起こること、そして、その分子機構には脱アデニル化複合体の構成因子が必要であることが明らかになった。
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