Article abstract
Nature Structural & Molecular Biology 16, 1134 - 1140 (2009)
Published online: 18 October 2009 | doi:10.1038/nsmb.1680
A two-pronged strategy to suppress host protein synthesis by SARS coronavirus Nsp1 protein
Wataru Kamitani1,2,3, Cheng Huang1,3, Krishna Narayanan1, Kumari G Lokugamage1 & Shinji Makino1
Abstract
Severe acute respiratory syndrome coronavirus nsp1 protein suppresses host gene expression, including type I interferon production, by promoting host mRNA degradation and inhibiting host translation, in infected cells. We present evidence that nsp1 uses a novel, two-pronged strategy to inhibit host translation and gene expression. Nsp1 bound to the 40S ribosomal subunit and inactivated the translational activity of the 40S subunits. Furthermore, the nsp1–40S ribosome complex induced the modification of the 5' region of capped mRNA template and rendered the template RNA translationally incompetent. Nsp1 also induced RNA cleavage in templates carrying the internal ribosome entry site (IRES) from encephalomyocarditis virus, but not in those carrying IRES elements from hepatitis C or cricket paralysis viruses, demonstrating that the nsp1-induced RNA modification was template-dependent. We speculate that the mRNAs that underwent the nsp1-mediated modification are marked for rapid turnover by the host RNA degradation machinery.
- Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, Texas, USA.
- Present address: Global Centers of Excellence Program, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
- These authors contributed equally to this work.
Correspondence to: Shinji Makino1 e-mail: shmakino@utmb.edu
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