| Project/Area Number |
18K06628
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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 47030:Pharmaceutical hygiene and biochemistry-related
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| Research Institution | Kumamoto University |
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Principal Investigator |
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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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | Nef / CLK / HIV / HIV-1 |
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| Outline of Final Research Achievements |
Nef, a virulence factor of HIV-1, is translated from the multiple-spliced 2-kb mRNAs transcribed from HIV-1 genome. In this study, we investigated critical region in 5’UTR of a nef mRNA for Nef expression, which was named as Nef-expression essential region (NER). We found that particular two nucleotide sequences, known as SR binding sequences, in the NER of nef mRNA are particularly important for the efficient Nef expression. Interestingly, treatment of TG003 known as CLK inhibitor induced to increase the Nef expression from nef mRNA in HEK293 cells, and the mutation within the particular two nucleotide sequence sites resulted in attenuation of the increase of Nef expression by TG003 treatment. Additionally, the NER was associated with efficient nef mRNA nuclear export. These results suggests that axis of CLK1-SR protein-the particular two nucleotide sequences in the NER is critical role for efficient Nef expression from nef mRNAs.
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| Academic Significance and Societal Importance of the Research Achievements |
NefのmRNAは700ヌクレオチド以上ある比較的長い5’UTRを持つが、本研究により、これまでに知られていなかったNef発現に重要な機構の一端を明らかにすることができた。この機構はNef発現抑制のための新しい標的となる可能性がある。Nef発現の抑制はHIV-1感染細胞の免疫による排除を亢進させることにつながる可能性があり、治癒を目指したHIV感染症の新たな治療戦略構築につながることが期待される。
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