A two-pronged strategy to suppress host protein synthesis by SARS coronavirus Nsp1 protein

Wataru Kamitani, Cheng Huang, Krishna Narayanan, Kumari G. Lokugamage, Shinji Makino

Research output: Contribution to journalArticle

79 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1134-1140
Number of pages7
JournalNature Structural and Molecular Biology
Volume16
Issue number11
DOIs
StatePublished - Nov 2009

Fingerprint

RNA Stability
Eukaryotic Small Ribosome Subunits
RNA Cleavage
RNA
Encephalomyocarditis virus
Gene Expression
Gryllidae
Severe Acute Respiratory Syndrome
Interferon Type I
Messenger RNA
Coronavirus
Hepatitis C
Ribosomes
Paralysis
Proteins
Viruses
Internal Ribosome Entry Sites
SARS coronavirus Nsp1 protein

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

A two-pronged strategy to suppress host protein synthesis by SARS coronavirus Nsp1 protein. / Kamitani, Wataru; Huang, Cheng; Narayanan, Krishna; Lokugamage, Kumari G.; Makino, Shinji.

In: Nature Structural and Molecular Biology, Vol. 16, No. 11, 11.2009, p. 1134-1140.

Research output: Contribution to journalArticle

Kamitani, Wataru ; Huang, Cheng ; Narayanan, Krishna ; Lokugamage, Kumari G. ; Makino, Shinji. / A two-pronged strategy to suppress host protein synthesis by SARS coronavirus Nsp1 protein. In: Nature Structural and Molecular Biology. 2009 ; Vol. 16, No. 11. pp. 1134-1140.
@article{d943917907d4488c8fbc402b25ed26dd,
title = "A two-pronged strategy to suppress host protein synthesis by SARS coronavirus Nsp1 protein",
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.",
author = "Wataru Kamitani and Cheng Huang and Krishna Narayanan and Lokugamage, {Kumari G.} and Shinji Makino",
year = "2009",
month = "11",
doi = "10.1038/nsmb.1680",
language = "English (US)",
volume = "16",
pages = "1134--1140",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
publisher = "Nature Publishing Group",
number = "11",

}

TY - JOUR

T1 - A two-pronged strategy to suppress host protein synthesis by SARS coronavirus Nsp1 protein

AU - Kamitani, Wataru

AU - Huang, Cheng

AU - Narayanan, Krishna

AU - Lokugamage, Kumari G.

AU - Makino, Shinji

PY - 2009/11

Y1 - 2009/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=70350768988&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70350768988&partnerID=8YFLogxK

U2 - 10.1038/nsmb.1680

DO - 10.1038/nsmb.1680

M3 - Article

C2 - 19838190

AN - SCOPUS:70350768988

VL - 16

SP - 1134

EP - 1140

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

SN - 1545-9993

IS - 11

ER -