| Project/Area Number |
18K07173
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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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| Review Section |
Basic Section 49070:Immunology-related
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| Research Institution | Osaka University |
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Principal Investigator |
MAEDA KAZUHIKO 大阪大学, 免疫学フロンティア研究センター, 特任准教授(常勤) (20332869)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | RNA輸送 / 胚中心 / R-loop / AID / R-koop |
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| Outline of Final Research Achievements |
During transcription, a DNA-RNA hybrid (R-loop) is transiently formed. The newly transcripts must be rapidly released from the template DNA and transported to the cytoplasm via mRNA transporters. It has been suggested that activation-induced cytidine deaminase (AID) acts on the R-loop during transcription. We investigated whether GANP, a component of the mRNA export complex TREX-2 that interacts with AID, directly affects R-loop formation using antibodies against endogenous GANP. As a result, we were not able to identify it in the antibody gene region. In the future, we plan to investigate GANP mutants that capture transcription in a forced expression system.
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| Academic Significance and Societal Importance of the Research Achievements |
R-ループ形成は全ての遺伝子の転写時に通過するものであり、特に抗体遺伝子座ではB細胞の抗体産生を支える重要な仕組みの一つである。この仕組みの破堤は、容易くDNA損傷を招くとともに、他の細胞種では多数の疾患の要因ともなっている。R-ループから出た正常な転写物がmRNA輸送体へと運ばれていく一方で、mRNAの品質管理で異常となった転写物は、内在性のRNA分解酵素によって分解されて解消されていくと考えられている。本研究の成果は、基礎的解析に留まらず、遺伝的安定性の維持に関わるような疾患や調節機構の解明に繋がり、重要な役割を果たすと考えられる。
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