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Severe Acute Respiratory Syndrome Coronavirus Protein nsp1 Is a Novel Eukaryotic Translation Inhibitor That Represses Multiple Steps of Translation Initiation

Identifieur interne : 000958 ( PascalFrancis/Curation ); précédent : 000957; suivant : 000959

Severe Acute Respiratory Syndrome Coronavirus Protein nsp1 Is a Novel Eukaryotic Translation Inhibitor That Represses Multiple Steps of Translation Initiation

Auteurs : Kumari G. Lokugamage [États-Unis] ; Krishna Narayanan [États-Unis] ; CHENG HUANG [États-Unis] ; Shinji Makino [États-Unis]

Source :

RBID : Pascal:13-0027481

Descripteurs français

English descriptors

Abstract

Severe acute respiratory syndrome (SARS) coronavirus nonstructural protein 1 (nsp1) binds to the 40S ribosomal subunit and inhibits translation, and it also induces a template-dependent endonucleolytic cleavage of host mRNAs. nsp1 inhibits the translation of cap-dependent and internal ribosome entry site (IRES)-driven mRNAs, including SARS coronavirus mRNAs, hepatitis C virus (HCV), and cricket paralysis virus (CrPV) IRES-driven mRNAs that are resistant to nsp1-induced RNA cleavage. We used an nsp1 mutant, nsp1-CD, lacking the RNA cleavage function, to delineate the mechanism of nsp1-mediated translation inhibition and identify the translation step(s) targeted by nsp1. nsp1 and nsp1-CD had identical inhibitory effects on mRNA templates that are resistant to nsp1-induced RNA cleavage, implying the validity of using nsp1-CD to dissect the translation inhibition function of nsp1. We provide evidence for a novel mode of action of nsp1. nsp1 inhibited the translation initiation step by targeting at least two separate stages: 48S initiation complex formation and the steps involved in the formation of the 80S initiation complex from the 48S complex. nsp1 had a differential, mRNA template-dependent, inhibitory effect on 48S and 80S initiation complex formation. nsp1 inhibited different steps of translation initiation on CrPV and HCV IRES, both of which initiate translation via an IRES-40S binary complex intermediate; nsp1 inhibited binary complex formation on CrPV IRES and 48S complex formation on HCV IRES. Collectively, the data revealed that nsp1 inhibited translation by exerting its effect on multiple stages of translation initiation, depending on the mechanism of initiation operating on the mRNA template.
pA  
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A11 01  1    @1 LOKUGAMAGE (Kumari G.)
A11 02  1    @1 NARAYANAN (Krishna)
A11 03  1    @1 CHENG HUANG
A11 04  1    @1 MAKINO (Shinji)
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A14 03      @1 UTMB Center for Tropical Diseases, The University of Texas Medical Branch @2 Galveston, Texas @3 USA @Z 4 aut.
A14 04      @1 Sealy Centerfor Vaccine Development, The University of Texas Medical Branch @2 Galveston, Texas @3 USA @Z 4 aut.
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C01 01    ENG  @0 Severe acute respiratory syndrome (SARS) coronavirus nonstructural protein 1 (nsp1) binds to the 40S ribosomal subunit and inhibits translation, and it also induces a template-dependent endonucleolytic cleavage of host mRNAs. nsp1 inhibits the translation of cap-dependent and internal ribosome entry site (IRES)-driven mRNAs, including SARS coronavirus mRNAs, hepatitis C virus (HCV), and cricket paralysis virus (CrPV) IRES-driven mRNAs that are resistant to nsp1-induced RNA cleavage. We used an nsp1 mutant, nsp1-CD, lacking the RNA cleavage function, to delineate the mechanism of nsp1-mediated translation inhibition and identify the translation step(s) targeted by nsp1. nsp1 and nsp1-CD had identical inhibitory effects on mRNA templates that are resistant to nsp1-induced RNA cleavage, implying the validity of using nsp1-CD to dissect the translation inhibition function of nsp1. We provide evidence for a novel mode of action of nsp1. nsp1 inhibited the translation initiation step by targeting at least two separate stages: 48S initiation complex formation and the steps involved in the formation of the 80S initiation complex from the 48S complex. nsp1 had a differential, mRNA template-dependent, inhibitory effect on 48S and 80S initiation complex formation. nsp1 inhibited different steps of translation initiation on CrPV and HCV IRES, both of which initiate translation via an IRES-40S binary complex intermediate; nsp1 inhibited binary complex formation on CrPV IRES and 48S complex formation on HCV IRES. Collectively, the data revealed that nsp1 inhibited translation by exerting its effect on multiple stages of translation initiation, depending on the mechanism of initiation operating on the mRNA template.
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C03 04  X  SPA  @0 Iniciación traducción @5 07
C03 05  X  FRE  @0 Syndrome respiratoire aigu sévère @2 NM @5 14
C03 05  X  ENG  @0 Severe acute respiratory syndrome @2 NM @5 14
C03 05  X  SPA  @0 Síndrome respiratorio agudo severo @2 NM @5 14
C07 01  X  FRE  @0 Coronaviridae @2 NW
C07 01  X  ENG  @0 Coronaviridae @2 NW
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C07 02  X  FRE  @0 Nidovirales @2 NW
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C07 02  X  SPA  @0 Nidovirales @2 NW
C07 03  X  FRE  @0 Virus @2 NW
C07 03  X  ENG  @0 Virus @2 NW
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C07 04  X  FRE  @0 Pathologie de l'appareil respiratoire @5 13
C07 04  X  ENG  @0 Respiratory disease @5 13
C07 04  X  SPA  @0 Aparato respiratorio patología @5 13
C07 05  X  FRE  @0 Virose
C07 05  X  ENG  @0 Viral disease
C07 05  X  SPA  @0 Virosis
C07 06  X  FRE  @0 Infection
C07 06  X  ENG  @0 Infection
C07 06  X  SPA  @0 Infección
C07 07  X  FRE  @0 Pathologie des poumons @5 16
C07 07  X  ENG  @0 Lung disease @5 16
C07 07  X  SPA  @0 Pulmón patología @5 16
N21       @1 014
N44 01      @1 OTO
N82       @1 OTO

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Pascal:13-0027481

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<div type="abstract" xml:lang="en">Severe acute respiratory syndrome (SARS) coronavirus nonstructural protein 1 (nsp1) binds to the 40S ribosomal subunit and inhibits translation, and it also induces a template-dependent endonucleolytic cleavage of host mRNAs. nsp1 inhibits the translation of cap-dependent and internal ribosome entry site (IRES)-driven mRNAs, including SARS coronavirus mRNAs, hepatitis C virus (HCV), and cricket paralysis virus (CrPV) IRES-driven mRNAs that are resistant to nsp1-induced RNA cleavage. We used an nsp1 mutant, nsp1-CD, lacking the RNA cleavage function, to delineate the mechanism of nsp1-mediated translation inhibition and identify the translation step(s) targeted by nsp1. nsp1 and nsp1-CD had identical inhibitory effects on mRNA templates that are resistant to nsp1-induced RNA cleavage, implying the validity of using nsp1-CD to dissect the translation inhibition function of nsp1. We provide evidence for a novel mode of action of nsp1. nsp1 inhibited the translation initiation step by targeting at least two separate stages: 48S initiation complex formation and the steps involved in the formation of the 80S initiation complex from the 48S complex. nsp1 had a differential, mRNA template-dependent, inhibitory effect on 48S and 80S initiation complex formation. nsp1 inhibited different steps of translation initiation on CrPV and HCV IRES, both of which initiate translation via an IRES-40S binary complex intermediate; nsp1 inhibited binary complex formation on CrPV IRES and 48S complex formation on HCV IRES. Collectively, the data revealed that nsp1 inhibited translation by exerting its effect on multiple stages of translation initiation, depending on the mechanism of initiation operating on the mRNA template.</div>
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<fC03 i1="04" i2="X" l="SPA">
<s0>Iniciación traducción</s0>
<s5>07</s5>
</fC03>
<fC03 i1="05" i2="X" l="FRE">
<s0>Syndrome respiratoire aigu sévère</s0>
<s2>NM</s2>
<s5>14</s5>
</fC03>
<fC03 i1="05" i2="X" l="ENG">
<s0>Severe acute respiratory syndrome</s0>
<s2>NM</s2>
<s5>14</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA">
<s0>Síndrome respiratorio agudo severo</s0>
<s2>NM</s2>
<s5>14</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE">
<s0>Coronaviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="01" i2="X" l="ENG">
<s0>Coronaviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="01" i2="X" l="SPA">
<s0>Coronaviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="02" i2="X" l="FRE">
<s0>Nidovirales</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="02" i2="X" l="ENG">
<s0>Nidovirales</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="02" i2="X" l="SPA">
<s0>Nidovirales</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="03" i2="X" l="FRE">
<s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="03" i2="X" l="ENG">
<s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="03" i2="X" l="SPA">
<s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="04" i2="X" l="FRE">
<s0>Pathologie de l'appareil respiratoire</s0>
<s5>13</s5>
</fC07>
<fC07 i1="04" i2="X" l="ENG">
<s0>Respiratory disease</s0>
<s5>13</s5>
</fC07>
<fC07 i1="04" i2="X" l="SPA">
<s0>Aparato respiratorio patología</s0>
<s5>13</s5>
</fC07>
<fC07 i1="05" i2="X" l="FRE">
<s0>Virose</s0>
</fC07>
<fC07 i1="05" i2="X" l="ENG">
<s0>Viral disease</s0>
</fC07>
<fC07 i1="05" i2="X" l="SPA">
<s0>Virosis</s0>
</fC07>
<fC07 i1="06" i2="X" l="FRE">
<s0>Infection</s0>
</fC07>
<fC07 i1="06" i2="X" l="ENG">
<s0>Infection</s0>
</fC07>
<fC07 i1="06" i2="X" l="SPA">
<s0>Infección</s0>
</fC07>
<fC07 i1="07" i2="X" l="FRE">
<s0>Pathologie des poumons</s0>
<s5>16</s5>
</fC07>
<fC07 i1="07" i2="X" l="ENG">
<s0>Lung disease</s0>
<s5>16</s5>
</fC07>
<fC07 i1="07" i2="X" l="SPA">
<s0>Pulmón patología</s0>
<s5>16</s5>
</fC07>
<fN21>
<s1>014</s1>
</fN21>
<fN44 i1="01">
<s1>OTO</s1>
</fN44>
<fN82>
<s1>OTO</s1>
</fN82>
</pA>
</standard>
</inist>
</record>

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   |wiki=    Sante
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   |texte=   Severe Acute Respiratory Syndrome Coronavirus Protein nsp1 Is a Novel Eukaryotic Translation Inhibitor That Represses Multiple Steps of Translation Initiation
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