| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Outline of Final Research Achievements |
Post-transcriptional regulation that modifies mRNA stability and translation provides rapid and flexible control of gene expression and control of mRNA stability is important for coordinating the initiation and resolution of inflammation. However, the mechanisms of mRNA regulation in innate immune system remain to be clarified. This study is aiming to investigate the role of RNA helicase UPF1 in innate immune system. We generated LysM-Cre-UPF1Flox/Flox mice and found that UPF1 negatively regulated cytokine mRNAs such as IL6 and TNF by analyzing UPF1-deficient macrophages from LysM-Cre-UPF1Flox/Flox mice. Moreover, we found that UPF1 associated with Tristetraprolin (TTP), which is an RNA-binding protein and destabilize cytokine mRNAs such as TNF and CSF2 by targeting AU-rich elements in 3′ untranslated region, and UPF1 was required for the TTP-mediated mRNA decay. Our findings reveal that UPF1 plays a critical role in regulating cytokine mRNAs in innate immune system.
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