Severe Acute Respiratory Syndrome Coronavirus Protein nsp1 Is a Novel Eukaryotic Translation Inhibitor That Represses Multiple Steps of Translation Initiation
Identifieur interne : 000039 ( PascalFrancis/Checkpoint ); précédent : 000038; suivant : 000040Severe 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 :
- Journal of virology [ 0022-538X ] ; 2012.
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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.
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Lokugamage</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Microbiology and Immunology, The University of Texas Medical Branch</s1><s2>Galveston, Texas</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Narayanan, Krishna" sort="Narayanan, Krishna" uniqKey="Narayanan K" first="Krishna" last="Narayanan">Krishna Narayanan</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Microbiology and Immunology, The University of Texas Medical Branch</s1><s2>Galveston, Texas</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Cheng Huang" sort="Cheng Huang" uniqKey="Cheng Huang" last="Cheng Huang">CHENG HUANG</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Microbiology and Immunology, The University of Texas Medical Branch</s1><s2>Galveston, Texas</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Makino, Shinji" sort="Makino, Shinji" uniqKey="Makino S" first="Shinji" last="Makino">Shinji Makino</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Microbiology and Immunology, The University of Texas Medical Branch</s1><s2>Galveston, Texas</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Center for Biodefense and Emerging Infectious Diseases, The University of Texas Medical Branch</s1><s2>Galveston, Texas</s2><s3>USA</s3><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="03"><s1>UTMB Center for Tropical Diseases, The University of Texas Medical Branch</s1><s2>Galveston, Texas</s2><s3>USA</s3><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Sealy Centerfor Vaccine Development, The University of Texas Medical Branch</s1><s2>Galveston, Texas</s2><s3>USA</s3><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Texas</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">13-0027481</idno><date when="2012">2012</date><idno type="stanalyst">PASCAL 13-0027481 INIST</idno><idno type="RBID">Pascal:13-0027481</idno><idno type="wicri:Area/PascalFrancis/Corpus">000029</idno><idno type="wicri:Area/PascalFrancis/Curation">000958</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000039</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000039</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Severe Acute Respiratory Syndrome Coronavirus Protein nsp1 Is a Novel Eukaryotic Translation Inhibitor That Represses Multiple Steps of Translation Initiation</title><author><name sortKey="Lokugamage, Kumari G" sort="Lokugamage, Kumari G" uniqKey="Lokugamage K" first="Kumari G." last="Lokugamage">Kumari G. Lokugamage</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Microbiology and Immunology, The University of Texas Medical Branch</s1><s2>Galveston, Texas</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Narayanan, Krishna" sort="Narayanan, Krishna" uniqKey="Narayanan K" first="Krishna" last="Narayanan">Krishna Narayanan</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Microbiology and Immunology, The University of Texas Medical Branch</s1><s2>Galveston, Texas</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Cheng Huang" sort="Cheng Huang" uniqKey="Cheng Huang" last="Cheng Huang">CHENG HUANG</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Microbiology and Immunology, The University of Texas Medical Branch</s1><s2>Galveston, Texas</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Makino, Shinji" sort="Makino, Shinji" uniqKey="Makino S" first="Shinji" last="Makino">Shinji Makino</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Microbiology and Immunology, The University of Texas Medical Branch</s1><s2>Galveston, Texas</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Center for Biodefense and Emerging Infectious Diseases, The University of Texas Medical Branch</s1><s2>Galveston, Texas</s2><s3>USA</s3><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="03"><s1>UTMB Center for Tropical Diseases, The University of Texas Medical Branch</s1><s2>Galveston, Texas</s2><s3>USA</s3><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Sealy Centerfor Vaccine Development, The University of Texas Medical Branch</s1><s2>Galveston, Texas</s2><s3>USA</s3><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Texas</region></placeName></affiliation></author></analytic><series><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Coronavirus</term><term>Genetic translation</term><term>Protein</term><term>Severe acute respiratory syndrome</term><term>Translation initiation</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Coronavirus</term><term>Protéine</term><term>Traduction génétique</term><term>Initiation traduction</term><term>Syndrome respiratoire aigu sévère</term></keywords></textClass></profileDesc></teiHeader><front><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></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0022-538X</s0></fA01><fA03 i2="1"><s0>J. virol.</s0></fA03><fA05><s2>86</s2></fA05><fA06><s2>24</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Severe Acute Respiratory Syndrome Coronavirus Protein nsp1 Is a Novel Eukaryotic Translation Inhibitor That Represses Multiple Steps of Translation Initiation</s1></fA08><fA11 i1="01" i2="1"><s1>LOKUGAMAGE (Kumari G.)</s1></fA11><fA11 i1="02" i2="1"><s1>NARAYANAN (Krishna)</s1></fA11><fA11 i1="03" i2="1"><s1>CHENG HUANG</s1></fA11><fA11 i1="04" i2="1"><s1>MAKINO (Shinji)</s1></fA11><fA14 i1="01"><s1>Department of Microbiology and Immunology, The University of Texas Medical Branch</s1><s2>Galveston, Texas</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></fA14><fA14 i1="02"><s1>Center for Biodefense and Emerging Infectious Diseases, The University of Texas Medical Branch</s1><s2>Galveston, Texas</s2><s3>USA</s3><sZ>4 aut.</sZ></fA14><fA14 i1="03"><s1>UTMB Center for Tropical Diseases, The University of Texas Medical Branch</s1><s2>Galveston, Texas</s2><s3>USA</s3><sZ>4 aut.</sZ></fA14><fA14 i1="04"><s1>Sealy Centerfor Vaccine Development, The University of Texas Medical Branch</s1><s2>Galveston, Texas</s2><s3>USA</s3><sZ>4 aut.</sZ></fA14><fA20><s1>13598-13608</s1></fA20><fA21><s1>2012</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>13592</s2><s5>354000506222740410</s5></fA43><fA44><s0>0000</s0><s1>© 2013 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>39 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>13-0027481</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Journal of virology</s0></fA64><fA66 i1="01"><s0>USA</s0></fA66><fC01 i1="01" l="ENG"><s0>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.</s0></fC01><fC02 i1="01" i2="X"><s0>002A05C10</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Coronavirus</s0><s2>NW</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Coronavirus</s0><s2>NW</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Coronavirus</s0><s2>NW</s2><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Protéine</s0><s5>05</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Protein</s0><s5>05</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Proteína</s0><s5>05</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Traduction génétique</s0><s5>06</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Genetic translation</s0><s5>06</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Traducción genética</s0><s5>06</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Initiation traduction</s0><s5>07</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Translation initiation</s0><s5>07</s5></fC03><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><affiliations><list><country><li>États-Unis</li></country><region><li>Texas</li></region></list><tree><country name="États-Unis"><region name="Texas"><name sortKey="Lokugamage, Kumari G" sort="Lokugamage, Kumari G" uniqKey="Lokugamage K" first="Kumari G." last="Lokugamage">Kumari G. Lokugamage</name></region><name sortKey="Cheng Huang" sort="Cheng Huang" uniqKey="Cheng Huang" last="Cheng Huang">CHENG HUANG</name><name sortKey="Makino, Shinji" sort="Makino, Shinji" uniqKey="Makino S" first="Shinji" last="Makino">Shinji Makino</name><name sortKey="Makino, Shinji" sort="Makino, Shinji" uniqKey="Makino S" first="Shinji" last="Makino">Shinji Makino</name><name sortKey="Makino, Shinji" sort="Makino, Shinji" uniqKey="Makino S" first="Shinji" last="Makino">Shinji Makino</name><name sortKey="Makino, Shinji" sort="Makino, Shinji" uniqKey="Makino S" first="Shinji" last="Makino">Shinji Makino</name><name sortKey="Narayanan, Krishna" sort="Narayanan, Krishna" uniqKey="Narayanan K" first="Krishna" last="Narayanan">Krishna Narayanan</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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