Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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Research Abstract |
Severe acute respiratory syndrome coronavirus (SARS-CoV) is the etiological agent of a newly emerged disease. Nsp1 binds to 40S ribosome subunits, which causes a translational shutoff in the cells expressing nsp1. The nsp1-40S complex further induces an endonucleolytic RNA cleavage near the 5'UTR of host mRNA, resulting in the promotion of RNA decay. However, the mechanism by which nsp1-induced RNA cleavage is unknown. We identified Upf1 as a binding partner of nsp1 by pulldown purification and mass spectrometry. Upf1 is a predominantly cytoplasmic RNA-binding protein that is essential for nonsense-mediated RNA decay pathway. Coimmunoprecipitation analyses in transfected cells confirmed a specific interaction between nsp1 and Upf1. Small interfering RNA-mediated knockdown of Upf1 resulted in suppression of nsp1-mediated RNA cleavage. Our data indicate a novel mechanism of host mRNA cleavage by SARA-CoV nsp1 protein.
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