| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Outline of Final Research Achievements |
Nonsense-mediated mRNA decay (NMD) is a conserved cellular mRNA quality control mechanism. RNA signals to express viral genes potentially initiate NMD, nevertheless it is not clear how viruses evade NMD. Human-T-cell Leukemia Virus type-I (HTLV-1) is a retrovirus responsible for Adult T-cell Leukemia (ATL). Previously, we demonstrated that HTLV-1 Rex approves the stability of viral RNA by inhibiting NMD. In the present study, we focused on the molecular mechanism of NMD inhibition by Rex, and further clarified that the N-terminal region of Rex with unknown function (domain-X), was critical for effective suppression of NMD activity. We also showed that overexpression of Rex resulted in significant changes of more than 9,000 gene expression profiles in CEM human T cell line. Our results propose a possibility that Rex stabilizes the viral RNA by inhibition of NMD through the domain-X, and perturbs cellular mRNA metabolism and host cell homeostasis for its new function.
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