La-related Protein 1 (LARP1) Represses Terminal Oligopyrimidine (TOP) mRNA Translation Downstream of mTOR Complex 1 (mTORC1).
Identifieur interne : 000C76 ( Main/Exploration ); précédent : 000C75; suivant : 000C77La-related Protein 1 (LARP1) Represses Terminal Oligopyrimidine (TOP) mRNA Translation Downstream of mTOR Complex 1 (mTORC1).
Auteurs : Bruno D. Fonseca [Oman] ; Chadi Zakaria [Canada] ; Jian-Jun Jia [Canada] ; Tyson E. Graber [Canada] ; Yuri Svitkin [Canada] ; Soroush Tahmasebi [Canada] ; Danielle Healy [Canada] ; Huy-Dung Hoang [Canada] ; Jacob M. Jensen [Danemark] ; Ilo T. Diao [Danemark] ; Alexandre Lussier [Canada] ; Christopher Dajadian [Canada] ; Niranjan Padmanabhan [Canada] ; Walter Wang [Canada] ; Edna Matta-Camacho [Canada] ; Jaclyn Hearnden [Canada] ; Ewan M. Smith [Royaume-Uni] ; Yoshinori Tsukumo [Canada] ; Akiko Yanagiya [Canada] ; Masahiro Morita [Canada] ; Emmanuel Petroulakis [Canada] ; Jose L. González [Mexique] ; Greco Hernández [Mexique] ; Tommy Alain [Canada] ; Christian K. Damgaard [Danemark]Source :
- The Journal of biological chemistry [ 1083-351X ] ; 2015.
Descripteurs français
- KwdFr :
- ARN messager (composition chimique), ARN messager (génétique), ARN messager (métabolisme), Autoantigènes (génétique), Autoantigènes (métabolisme), Biosynthèse des protéines (MeSH), Complexe-1 cible mécanistique de la rapamycine (MeSH), Complexes multiprotéiques (génétique), Complexes multiprotéiques (métabolisme), Facteur-4E d'initiation eucaryote (génétique), Facteur-4E d'initiation eucaryote (métabolisme), Glycoprotéines membranaires (génétique), Glycoprotéines membranaires (métabolisme), Humains (MeSH), Liaison aux protéines (MeSH), Protéine de régulation associée à mTOR (MeSH), Protéines adaptatrices de la transduction du signal (génétique), Protéines adaptatrices de la transduction du signal (métabolisme), Ribonucléoprotéines (génétique), Ribonucléoprotéines (métabolisme), Régulation négative (MeSH), Sérine-thréonine kinases TOR (génétique), Sérine-thréonine kinases TOR (métabolisme).
- MESH :
- composition chimique : ARN messager.
- génétique : ARN messager, Autoantigènes, Complexes multiprotéiques, Facteur-4E d'initiation eucaryote, Glycoprotéines membranaires, Protéines adaptatrices de la transduction du signal, Ribonucléoprotéines, Sérine-thréonine kinases TOR.
- métabolisme : ARN messager, Autoantigènes, Complexes multiprotéiques, Facteur-4E d'initiation eucaryote, Glycoprotéines membranaires, Protéines adaptatrices de la transduction du signal, Ribonucléoprotéines, Sérine-thréonine kinases TOR.
- Biosynthèse des protéines, Complexe-1 cible mécanistique de la rapamycine, Humains, Liaison aux protéines, Protéine de régulation associée à mTOR, Régulation négative.
English descriptors
- KwdEn :
- Adaptor Proteins, Signal Transducing (genetics), Adaptor Proteins, Signal Transducing (metabolism), Autoantigens (genetics), Autoantigens (metabolism), Down-Regulation (MeSH), Eukaryotic Initiation Factor-4E (genetics), Eukaryotic Initiation Factor-4E (metabolism), Humans (MeSH), Mechanistic Target of Rapamycin Complex 1 (MeSH), Membrane Glycoproteins (genetics), Membrane Glycoproteins (metabolism), Multiprotein Complexes (genetics), Multiprotein Complexes (metabolism), Protein Binding (MeSH), Protein Biosynthesis (MeSH), RNA, Messenger (chemistry), RNA, Messenger (genetics), RNA, Messenger (metabolism), Regulatory-Associated Protein of mTOR (MeSH), Ribonucleoproteins (genetics), Ribonucleoproteins (metabolism), TOR Serine-Threonine Kinases (genetics), TOR Serine-Threonine Kinases (metabolism).
- MESH :
- chemical , chemistry : RNA, Messenger.
- chemical , genetics : Adaptor Proteins, Signal Transducing, Autoantigens, Eukaryotic Initiation Factor-4E, Membrane Glycoproteins, Multiprotein Complexes, RNA, Messenger, Ribonucleoproteins, TOR Serine-Threonine Kinases.
- chemical , metabolism : Adaptor Proteins, Signal Transducing, Autoantigens, Eukaryotic Initiation Factor-4E, Membrane Glycoproteins, Multiprotein Complexes, RNA, Messenger, Ribonucleoproteins, TOR Serine-Threonine Kinases.
- Down-Regulation, Humans, Mechanistic Target of Rapamycin Complex 1, Protein Binding, Protein Biosynthesis, Regulatory-Associated Protein of mTOR.
Abstract
The mammalian target of rapamycin complex 1 (mTORC1) is a critical regulator of protein synthesis. The best studied targets of mTORC1 in translation are the eukaryotic initiation factor-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase 1 (S6K1). In this study, we identify the La-related protein 1 (LARP1) as a key novel target of mTORC1 with a fundamental role in terminal oligopyrimidine (TOP) mRNA translation. Recent genome-wide studies indicate that TOP and TOP-like mRNAs compose a large portion of the mTORC1 translatome, but the mechanism by which mTORC1 controls TOP mRNA translation is incompletely understood. Here, we report that LARP1 functions as a key repressor of TOP mRNA translation downstream of mTORC1. Our data show the following: (i) LARP1 associates with mTORC1 via RAPTOR; (ii) LARP1 interacts with TOP mRNAs in an mTORC1-dependent manner; (iii) LARP1 binds the 5'TOP motif to repress TOP mRNA translation; and (iv) LARP1 competes with the eukaryotic initiation factor (eIF) 4G for TOP mRNA binding. Importantly, from a drug resistance standpoint, our data also show that reducing LARP1 protein levels by RNA interference attenuates the inhibitory effect of rapamycin, Torin1, and amino acid deprivation on TOP mRNA translation. Collectively, our findings demonstrate that LARP1 functions as an important repressor of TOP mRNA translation downstream of mTORC1.
DOI: 10.1074/jbc.M114.621730
PubMed: 25940091
PubMed Central: PMC4481205
Affiliations:
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Fonseca</name><affiliation wicri:level="1"><nlm:affiliation>From the Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8L1, Canada, brunodfonseca@gmail.com.</nlm:affiliation><country wicri:rule="url">Oman</country><wicri:regionArea>From the Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8L1, Canada</wicri:regionArea><wicri:noRegion>Canada</wicri:noRegion></affiliation></author><author><name sortKey="Zakaria, Chadi" sort="Zakaria, Chadi" uniqKey="Zakaria C" first="Chadi" last="Zakaria">Chadi Zakaria</name><affiliation wicri:level="4"><nlm:affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Jia, Jian Jun" sort="Jia, Jian Jun" uniqKey="Jia J" first="Jian-Jun" last="Jia">Jian-Jun Jia</name><affiliation wicri:level="1"><nlm:affiliation>From the Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8L1, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>From the Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8L1</wicri:regionArea><wicri:noRegion>Ontario K1H 8L1</wicri:noRegion></affiliation></author><author><name sortKey="Graber, Tyson E" sort="Graber, Tyson E" uniqKey="Graber T" first="Tyson E" last="Graber">Tyson E. Graber</name><affiliation wicri:level="1"><nlm:affiliation>From the Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8L1, Canada, the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>From the Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8L1, Canada, the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3</wicri:regionArea><wicri:noRegion>Quebec H3A 1A3</wicri:noRegion></affiliation></author><author><name sortKey="Svitkin, Yuri" sort="Svitkin, Yuri" uniqKey="Svitkin Y" first="Yuri" last="Svitkin">Yuri Svitkin</name><affiliation wicri:level="4"><nlm:affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Tahmasebi, Soroush" sort="Tahmasebi, Soroush" uniqKey="Tahmasebi S" first="Soroush" last="Tahmasebi">Soroush Tahmasebi</name><affiliation wicri:level="4"><nlm:affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Healy, Danielle" sort="Healy, Danielle" uniqKey="Healy D" first="Danielle" last="Healy">Danielle Healy</name><affiliation wicri:level="1"><nlm:affiliation>From the Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8L1, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>From the Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8L1</wicri:regionArea><wicri:noRegion>Ontario K1H 8L1</wicri:noRegion></affiliation></author><author><name sortKey="Hoang, Huy Dung" sort="Hoang, Huy Dung" uniqKey="Hoang H" first="Huy-Dung" last="Hoang">Huy-Dung Hoang</name><affiliation wicri:level="1"><nlm:affiliation>From the Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8L1, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>From the Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8L1</wicri:regionArea><wicri:noRegion>Ontario K1H 8L1</wicri:noRegion></affiliation></author><author><name sortKey="Jensen, Jacob M" sort="Jensen, Jacob M" uniqKey="Jensen J" first="Jacob M" last="Jensen">Jacob M. Jensen</name><affiliation wicri:level="1"><nlm:affiliation>the Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus C, Denmark.</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>the Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus C</wicri:regionArea><wicri:noRegion>DK-8000 Aarhus C</wicri:noRegion></affiliation></author><author><name sortKey="Diao, Ilo T" sort="Diao, Ilo T" uniqKey="Diao I" first="Ilo T" last="Diao">Ilo T. Diao</name><affiliation wicri:level="1"><nlm:affiliation>the Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus C, Denmark.</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>the Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus C</wicri:regionArea><wicri:noRegion>DK-8000 Aarhus C</wicri:noRegion></affiliation></author><author><name sortKey="Lussier, Alexandre" sort="Lussier, Alexandre" uniqKey="Lussier A" first="Alexandre" last="Lussier">Alexandre Lussier</name><affiliation wicri:level="4"><nlm:affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Dajadian, Christopher" sort="Dajadian, Christopher" uniqKey="Dajadian C" first="Christopher" last="Dajadian">Christopher Dajadian</name><affiliation wicri:level="4"><nlm:affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Padmanabhan, Niranjan" sort="Padmanabhan, Niranjan" uniqKey="Padmanabhan N" first="Niranjan" last="Padmanabhan">Niranjan Padmanabhan</name><affiliation wicri:level="4"><nlm:affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Wang, Walter" sort="Wang, Walter" uniqKey="Wang W" first="Walter" last="Wang">Walter Wang</name><affiliation wicri:level="4"><nlm:affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Matta Camacho, Edna" sort="Matta Camacho, Edna" uniqKey="Matta Camacho E" first="Edna" last="Matta-Camacho">Edna Matta-Camacho</name><affiliation wicri:level="4"><nlm:affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Hearnden, Jaclyn" sort="Hearnden, Jaclyn" uniqKey="Hearnden J" first="Jaclyn" last="Hearnden">Jaclyn Hearnden</name><affiliation wicri:level="4"><nlm:affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Smith, Ewan M" sort="Smith, Ewan M" uniqKey="Smith E" first="Ewan M" last="Smith">Ewan M. Smith</name><affiliation wicri:level="1"><nlm:affiliation>the Medical Research Council Toxicology Unit, Hodgkin Building, Lancaster Road, Leicester LE1 9HN, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>the Medical Research Council Toxicology Unit, Hodgkin Building, Lancaster Road, Leicester LE1 9HN</wicri:regionArea><wicri:noRegion>Leicester LE1 9HN</wicri:noRegion></affiliation></author><author><name sortKey="Tsukumo, Yoshinori" sort="Tsukumo, Yoshinori" uniqKey="Tsukumo Y" first="Yoshinori" last="Tsukumo">Yoshinori Tsukumo</name><affiliation wicri:level="4"><nlm:affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Yanagiya, Akiko" sort="Yanagiya, Akiko" uniqKey="Yanagiya A" first="Akiko" last="Yanagiya">Akiko Yanagiya</name><affiliation wicri:level="4"><nlm:affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Morita, Masahiro" sort="Morita, Masahiro" uniqKey="Morita M" first="Masahiro" last="Morita">Masahiro Morita</name><affiliation wicri:level="4"><nlm:affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Petroulakis, Emmanuel" sort="Petroulakis, Emmanuel" uniqKey="Petroulakis E" first="Emmanuel" last="Petroulakis">Emmanuel Petroulakis</name><affiliation wicri:level="4"><nlm:affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada, Pfizer Canada Inc., Kirkland, Quebec H9J 2M5, Canada, and.</nlm:affiliation><orgName type="university">Université McGill</orgName><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Gonzalez, Jose L" sort="Gonzalez, Jose L" uniqKey="Gonzalez J" first="Jose L" last="González">Jose L. González</name><affiliation wicri:level="1"><nlm:affiliation>the Division of Basic Science, National Institute of Cancer, 22 San Fernando Ave., Tlalpan, Mexico City 14080, Mexico.</nlm:affiliation><country xml:lang="fr">Mexique</country><wicri:regionArea>the Division of Basic Science, National Institute of Cancer, 22 San Fernando Ave., Tlalpan, Mexico City 14080</wicri:regionArea><wicri:noRegion>Mexico City 14080</wicri:noRegion></affiliation></author><author><name sortKey="Hernandez, Greco" sort="Hernandez, Greco" uniqKey="Hernandez G" first="Greco" last="Hernández">Greco Hernández</name><affiliation wicri:level="1"><nlm:affiliation>the Division of Basic Science, National Institute of Cancer, 22 San Fernando Ave., Tlalpan, Mexico City 14080, Mexico.</nlm:affiliation><country xml:lang="fr">Mexique</country><wicri:regionArea>the Division of Basic Science, National Institute of Cancer, 22 San Fernando Ave., Tlalpan, Mexico City 14080</wicri:regionArea><wicri:noRegion>Mexico City 14080</wicri:noRegion></affiliation></author><author><name sortKey="Alain, Tommy" sort="Alain, Tommy" uniqKey="Alain T" first="Tommy" last="Alain">Tommy Alain</name><affiliation wicri:level="1"><nlm:affiliation>From the Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8L1, Canada, tommy@arc.cheo.ca.</nlm:affiliation><country wicri:rule="url">Canada</country><wicri:regionArea>From the Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8L1, Canada</wicri:regionArea><wicri:noRegion>Canada</wicri:noRegion></affiliation></author><author><name sortKey="Damgaard, Christian K" sort="Damgaard, Christian K" uniqKey="Damgaard C" first="Christian K" last="Damgaard">Christian K. Damgaard</name><affiliation wicri:level="1"><nlm:affiliation>the Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus C, Denmark, ckd@mbg.au.dk.</nlm:affiliation><country wicri:rule="url">Danemark</country><wicri:regionArea>the Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus C, Denmark</wicri:regionArea><wicri:noRegion>Denmark</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2015">2015</date><idno type="RBID">pubmed:25940091</idno><idno type="pmid">25940091</idno><idno type="doi">10.1074/jbc.M114.621730</idno><idno type="pmc">PMC4481205</idno><idno type="wicri:Area/Main/Corpus">000C65</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000C65</idno><idno type="wicri:Area/Main/Curation">000C65</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000C65</idno><idno type="wicri:Area/Main/Exploration">000C65</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">La-related Protein 1 (LARP1) Represses Terminal Oligopyrimidine (TOP) mRNA Translation Downstream of mTOR Complex 1 (mTORC1).</title><author><name sortKey="Fonseca, Bruno D" sort="Fonseca, Bruno D" uniqKey="Fonseca B" first="Bruno D" last="Fonseca">Bruno D. Fonseca</name><affiliation wicri:level="1"><nlm:affiliation>From the Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8L1, Canada, brunodfonseca@gmail.com.</nlm:affiliation><country wicri:rule="url">Oman</country><wicri:regionArea>From the Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8L1, Canada</wicri:regionArea><wicri:noRegion>Canada</wicri:noRegion></affiliation></author><author><name sortKey="Zakaria, Chadi" sort="Zakaria, Chadi" uniqKey="Zakaria C" first="Chadi" last="Zakaria">Chadi Zakaria</name><affiliation wicri:level="4"><nlm:affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Jia, Jian Jun" sort="Jia, Jian Jun" uniqKey="Jia J" first="Jian-Jun" last="Jia">Jian-Jun Jia</name><affiliation wicri:level="1"><nlm:affiliation>From the Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8L1, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>From the Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8L1</wicri:regionArea><wicri:noRegion>Ontario K1H 8L1</wicri:noRegion></affiliation></author><author><name sortKey="Graber, Tyson E" sort="Graber, Tyson E" uniqKey="Graber T" first="Tyson E" last="Graber">Tyson E. Graber</name><affiliation wicri:level="1"><nlm:affiliation>From the Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8L1, Canada, the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>From the Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8L1, Canada, the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3</wicri:regionArea><wicri:noRegion>Quebec H3A 1A3</wicri:noRegion></affiliation></author><author><name sortKey="Svitkin, Yuri" sort="Svitkin, Yuri" uniqKey="Svitkin Y" first="Yuri" last="Svitkin">Yuri Svitkin</name><affiliation wicri:level="4"><nlm:affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Tahmasebi, Soroush" sort="Tahmasebi, Soroush" uniqKey="Tahmasebi S" first="Soroush" last="Tahmasebi">Soroush Tahmasebi</name><affiliation wicri:level="4"><nlm:affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Healy, Danielle" sort="Healy, Danielle" uniqKey="Healy D" first="Danielle" last="Healy">Danielle Healy</name><affiliation wicri:level="1"><nlm:affiliation>From the Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8L1, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>From the Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8L1</wicri:regionArea><wicri:noRegion>Ontario K1H 8L1</wicri:noRegion></affiliation></author><author><name sortKey="Hoang, Huy Dung" sort="Hoang, Huy Dung" uniqKey="Hoang H" first="Huy-Dung" last="Hoang">Huy-Dung Hoang</name><affiliation wicri:level="1"><nlm:affiliation>From the Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8L1, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>From the Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8L1</wicri:regionArea><wicri:noRegion>Ontario K1H 8L1</wicri:noRegion></affiliation></author><author><name sortKey="Jensen, Jacob M" sort="Jensen, Jacob M" uniqKey="Jensen J" first="Jacob M" last="Jensen">Jacob M. Jensen</name><affiliation wicri:level="1"><nlm:affiliation>the Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus C, Denmark.</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>the Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus C</wicri:regionArea><wicri:noRegion>DK-8000 Aarhus C</wicri:noRegion></affiliation></author><author><name sortKey="Diao, Ilo T" sort="Diao, Ilo T" uniqKey="Diao I" first="Ilo T" last="Diao">Ilo T. Diao</name><affiliation wicri:level="1"><nlm:affiliation>the Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus C, Denmark.</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>the Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus C</wicri:regionArea><wicri:noRegion>DK-8000 Aarhus C</wicri:noRegion></affiliation></author><author><name sortKey="Lussier, Alexandre" sort="Lussier, Alexandre" uniqKey="Lussier A" first="Alexandre" last="Lussier">Alexandre Lussier</name><affiliation wicri:level="4"><nlm:affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Dajadian, Christopher" sort="Dajadian, Christopher" uniqKey="Dajadian C" first="Christopher" last="Dajadian">Christopher Dajadian</name><affiliation wicri:level="4"><nlm:affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Padmanabhan, Niranjan" sort="Padmanabhan, Niranjan" uniqKey="Padmanabhan N" first="Niranjan" last="Padmanabhan">Niranjan Padmanabhan</name><affiliation wicri:level="4"><nlm:affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Wang, Walter" sort="Wang, Walter" uniqKey="Wang W" first="Walter" last="Wang">Walter Wang</name><affiliation wicri:level="4"><nlm:affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Matta Camacho, Edna" sort="Matta Camacho, Edna" uniqKey="Matta Camacho E" first="Edna" last="Matta-Camacho">Edna Matta-Camacho</name><affiliation wicri:level="4"><nlm:affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Hearnden, Jaclyn" sort="Hearnden, Jaclyn" uniqKey="Hearnden J" first="Jaclyn" last="Hearnden">Jaclyn Hearnden</name><affiliation wicri:level="4"><nlm:affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Smith, Ewan M" sort="Smith, Ewan M" uniqKey="Smith E" first="Ewan M" last="Smith">Ewan M. Smith</name><affiliation wicri:level="1"><nlm:affiliation>the Medical Research Council Toxicology Unit, Hodgkin Building, Lancaster Road, Leicester LE1 9HN, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>the Medical Research Council Toxicology Unit, Hodgkin Building, Lancaster Road, Leicester LE1 9HN</wicri:regionArea><wicri:noRegion>Leicester LE1 9HN</wicri:noRegion></affiliation></author><author><name sortKey="Tsukumo, Yoshinori" sort="Tsukumo, Yoshinori" uniqKey="Tsukumo Y" first="Yoshinori" last="Tsukumo">Yoshinori Tsukumo</name><affiliation wicri:level="4"><nlm:affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Yanagiya, Akiko" sort="Yanagiya, Akiko" uniqKey="Yanagiya A" first="Akiko" last="Yanagiya">Akiko Yanagiya</name><affiliation wicri:level="4"><nlm:affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Morita, Masahiro" sort="Morita, Masahiro" uniqKey="Morita M" first="Masahiro" last="Morita">Masahiro Morita</name><affiliation wicri:level="4"><nlm:affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Petroulakis, Emmanuel" sort="Petroulakis, Emmanuel" uniqKey="Petroulakis E" first="Emmanuel" last="Petroulakis">Emmanuel Petroulakis</name><affiliation wicri:level="4"><nlm:affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada, Pfizer Canada Inc., Kirkland, Quebec H9J 2M5, Canada, and.</nlm:affiliation><orgName type="university">Université McGill</orgName><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Gonzalez, Jose L" sort="Gonzalez, Jose L" uniqKey="Gonzalez J" first="Jose L" last="González">Jose L. González</name><affiliation wicri:level="1"><nlm:affiliation>the Division of Basic Science, National Institute of Cancer, 22 San Fernando Ave., Tlalpan, Mexico City 14080, Mexico.</nlm:affiliation><country xml:lang="fr">Mexique</country><wicri:regionArea>the Division of Basic Science, National Institute of Cancer, 22 San Fernando Ave., Tlalpan, Mexico City 14080</wicri:regionArea><wicri:noRegion>Mexico City 14080</wicri:noRegion></affiliation></author><author><name sortKey="Hernandez, Greco" sort="Hernandez, Greco" uniqKey="Hernandez G" first="Greco" last="Hernández">Greco Hernández</name><affiliation wicri:level="1"><nlm:affiliation>the Division of Basic Science, National Institute of Cancer, 22 San Fernando Ave., Tlalpan, Mexico City 14080, Mexico.</nlm:affiliation><country xml:lang="fr">Mexique</country><wicri:regionArea>the Division of Basic Science, National Institute of Cancer, 22 San Fernando Ave., Tlalpan, Mexico City 14080</wicri:regionArea><wicri:noRegion>Mexico City 14080</wicri:noRegion></affiliation></author><author><name sortKey="Alain, Tommy" sort="Alain, Tommy" uniqKey="Alain T" first="Tommy" last="Alain">Tommy Alain</name><affiliation wicri:level="1"><nlm:affiliation>From the Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8L1, Canada, tommy@arc.cheo.ca.</nlm:affiliation><country wicri:rule="url">Canada</country><wicri:regionArea>From the Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8L1, Canada</wicri:regionArea><wicri:noRegion>Canada</wicri:noRegion></affiliation></author><author><name sortKey="Damgaard, Christian K" sort="Damgaard, Christian K" uniqKey="Damgaard C" first="Christian K" last="Damgaard">Christian K. Damgaard</name><affiliation wicri:level="1"><nlm:affiliation>the Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus C, Denmark, ckd@mbg.au.dk.</nlm:affiliation><country wicri:rule="url">Danemark</country><wicri:regionArea>the Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus C, Denmark</wicri:regionArea><wicri:noRegion>Denmark</wicri:noRegion></affiliation></author></analytic><series><title level="j">The Journal of biological chemistry</title><idno type="eISSN">1083-351X</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adaptor Proteins, Signal Transducing (genetics)</term><term>Adaptor Proteins, Signal Transducing (metabolism)</term><term>Autoantigens (genetics)</term><term>Autoantigens (metabolism)</term><term>Down-Regulation (MeSH)</term><term>Eukaryotic Initiation Factor-4E (genetics)</term><term>Eukaryotic Initiation Factor-4E (metabolism)</term><term>Humans (MeSH)</term><term>Mechanistic Target of Rapamycin Complex 1 (MeSH)</term><term>Membrane Glycoproteins (genetics)</term><term>Membrane Glycoproteins (metabolism)</term><term>Multiprotein Complexes (genetics)</term><term>Multiprotein Complexes (metabolism)</term><term>Protein Binding (MeSH)</term><term>Protein Biosynthesis (MeSH)</term><term>RNA, Messenger (chemistry)</term><term>RNA, Messenger (genetics)</term><term>RNA, Messenger (metabolism)</term><term>Regulatory-Associated Protein of mTOR (MeSH)</term><term>Ribonucleoproteins (genetics)</term><term>Ribonucleoproteins (metabolism)</term><term>TOR Serine-Threonine Kinases (genetics)</term><term>TOR Serine-Threonine Kinases (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ARN messager (composition chimique)</term><term>ARN messager (génétique)</term><term>ARN messager (métabolisme)</term><term>Autoantigènes (génétique)</term><term>Autoantigènes (métabolisme)</term><term>Biosynthèse des protéines (MeSH)</term><term>Complexe-1 cible mécanistique de la rapamycine (MeSH)</term><term>Complexes multiprotéiques (génétique)</term><term>Complexes multiprotéiques (métabolisme)</term><term>Facteur-4E d'initiation eucaryote (génétique)</term><term>Facteur-4E d'initiation eucaryote (métabolisme)</term><term>Glycoprotéines membranaires (génétique)</term><term>Glycoprotéines membranaires (métabolisme)</term><term>Humains (MeSH)</term><term>Liaison aux protéines (MeSH)</term><term>Protéine de régulation associée à mTOR (MeSH)</term><term>Protéines adaptatrices de la transduction du signal (génétique)</term><term>Protéines adaptatrices de la transduction du signal (métabolisme)</term><term>Ribonucléoprotéines (génétique)</term><term>Ribonucléoprotéines (métabolisme)</term><term>Régulation négative (MeSH)</term><term>Sérine-thréonine kinases TOR (génétique)</term><term>Sérine-thréonine kinases TOR (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>RNA, Messenger</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Adaptor Proteins, Signal Transducing</term><term>Autoantigens</term><term>Eukaryotic Initiation Factor-4E</term><term>Membrane Glycoproteins</term><term>Multiprotein Complexes</term><term>RNA, Messenger</term><term>Ribonucleoproteins</term><term>TOR Serine-Threonine Kinases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Adaptor Proteins, Signal Transducing</term><term>Autoantigens</term><term>Eukaryotic Initiation Factor-4E</term><term>Membrane Glycoproteins</term><term>Multiprotein Complexes</term><term>RNA, Messenger</term><term>Ribonucleoproteins</term><term>TOR Serine-Threonine Kinases</term></keywords><keywords scheme="MESH" qualifier="composition chimique" xml:lang="fr"><term>ARN messager</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>ARN messager</term><term>Autoantigènes</term><term>Complexes multiprotéiques</term><term>Facteur-4E d'initiation eucaryote</term><term>Glycoprotéines membranaires</term><term>Protéines adaptatrices de la transduction du signal</term><term>Ribonucléoprotéines</term><term>Sérine-thréonine kinases TOR</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>ARN messager</term><term>Autoantigènes</term><term>Complexes multiprotéiques</term><term>Facteur-4E d'initiation eucaryote</term><term>Glycoprotéines membranaires</term><term>Protéines adaptatrices de la transduction du signal</term><term>Ribonucléoprotéines</term><term>Sérine-thréonine kinases TOR</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Down-Regulation</term><term>Humans</term><term>Mechanistic Target of Rapamycin Complex 1</term><term>Protein Binding</term><term>Protein Biosynthesis</term><term>Regulatory-Associated Protein of mTOR</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Biosynthèse des protéines</term><term>Complexe-1 cible mécanistique de la rapamycine</term><term>Humains</term><term>Liaison aux protéines</term><term>Protéine de régulation associée à mTOR</term><term>Régulation négative</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The mammalian target of rapamycin complex 1 (mTORC1) is a critical regulator of protein synthesis. The best studied targets of mTORC1 in translation are the eukaryotic initiation factor-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase 1 (S6K1). In this study, we identify the La-related protein 1 (LARP1) as a key novel target of mTORC1 with a fundamental role in terminal oligopyrimidine (TOP) mRNA translation. Recent genome-wide studies indicate that TOP and TOP-like mRNAs compose a large portion of the mTORC1 translatome, but the mechanism by which mTORC1 controls TOP mRNA translation is incompletely understood. Here, we report that LARP1 functions as a key repressor of TOP mRNA translation downstream of mTORC1. Our data show the following: (i) LARP1 associates with mTORC1 via RAPTOR; (ii) LARP1 interacts with TOP mRNAs in an mTORC1-dependent manner; (iii) LARP1 binds the 5'TOP motif to repress TOP mRNA translation; and (iv) LARP1 competes with the eukaryotic initiation factor (eIF) 4G for TOP mRNA binding. Importantly, from a drug resistance standpoint, our data also show that reducing LARP1 protein levels by RNA interference attenuates the inhibitory effect of rapamycin, Torin1, and amino acid deprivation on TOP mRNA translation. Collectively, our findings demonstrate that LARP1 functions as an important repressor of TOP mRNA translation downstream of mTORC1. </div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">25940091</PMID><DateCompleted><Year>2015</Year><Month>10</Month><Day>02</Day></DateCompleted><DateRevised><Year>2018</Year><Month>11</Month><Day>13</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1083-351X</ISSN><JournalIssue CitedMedium="Internet"><Volume>290</Volume><Issue>26</Issue><PubDate><Year>2015</Year><Month>Jun</Month><Day>26</Day></PubDate></JournalIssue><Title>The Journal of biological chemistry</Title><ISOAbbreviation>J Biol Chem</ISOAbbreviation></Journal><ArticleTitle>La-related Protein 1 (LARP1) Represses Terminal Oligopyrimidine (TOP) mRNA Translation Downstream of mTOR Complex 1 (mTORC1).</ArticleTitle><Pagination><MedlinePgn>15996-6020</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1074/jbc.M114.621730</ELocationID><Abstract><AbstractText>The mammalian target of rapamycin complex 1 (mTORC1) is a critical regulator of protein synthesis. The best studied targets of mTORC1 in translation are the eukaryotic initiation factor-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase 1 (S6K1). In this study, we identify the La-related protein 1 (LARP1) as a key novel target of mTORC1 with a fundamental role in terminal oligopyrimidine (TOP) mRNA translation. Recent genome-wide studies indicate that TOP and TOP-like mRNAs compose a large portion of the mTORC1 translatome, but the mechanism by which mTORC1 controls TOP mRNA translation is incompletely understood. Here, we report that LARP1 functions as a key repressor of TOP mRNA translation downstream of mTORC1. Our data show the following: (i) LARP1 associates with mTORC1 via RAPTOR; (ii) LARP1 interacts with TOP mRNAs in an mTORC1-dependent manner; (iii) LARP1 binds the 5'TOP motif to repress TOP mRNA translation; and (iv) LARP1 competes with the eukaryotic initiation factor (eIF) 4G for TOP mRNA binding. Importantly, from a drug resistance standpoint, our data also show that reducing LARP1 protein levels by RNA interference attenuates the inhibitory effect of rapamycin, Torin1, and amino acid deprivation on TOP mRNA translation. Collectively, our findings demonstrate that LARP1 functions as an important repressor of TOP mRNA translation downstream of mTORC1. </AbstractText><CopyrightInformation>© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Fonseca</LastName><ForeName>Bruno D</ForeName><Initials>BD</Initials><AffiliationInfo><Affiliation>From the Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8L1, Canada, brunodfonseca@gmail.com.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zakaria</LastName><ForeName>Chadi</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jia</LastName><ForeName>Jian-Jun</ForeName><Initials>JJ</Initials><AffiliationInfo><Affiliation>From the Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8L1, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Graber</LastName><ForeName>Tyson E</ForeName><Initials>TE</Initials><AffiliationInfo><Affiliation>From the Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8L1, Canada, the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Svitkin</LastName><ForeName>Yuri</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tahmasebi</LastName><ForeName>Soroush</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Healy</LastName><ForeName>Danielle</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>From the Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8L1, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hoang</LastName><ForeName>Huy-Dung</ForeName><Initials>HD</Initials><AffiliationInfo><Affiliation>From the Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8L1, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jensen</LastName><ForeName>Jacob M</ForeName><Initials>JM</Initials><AffiliationInfo><Affiliation>the Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus C, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Diao</LastName><ForeName>Ilo T</ForeName><Initials>IT</Initials><AffiliationInfo><Affiliation>the Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus C, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lussier</LastName><ForeName>Alexandre</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dajadian</LastName><ForeName>Christopher</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Padmanabhan</LastName><ForeName>Niranjan</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Walter</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Matta-Camacho</LastName><ForeName>Edna</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hearnden</LastName><ForeName>Jaclyn</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Smith</LastName><ForeName>Ewan M</ForeName><Initials>EM</Initials><AffiliationInfo><Affiliation>the Medical Research Council Toxicology Unit, Hodgkin Building, Lancaster Road, Leicester LE1 9HN, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tsukumo</LastName><ForeName>Yoshinori</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yanagiya</LastName><ForeName>Akiko</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Morita</LastName><ForeName>Masahiro</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Petroulakis</LastName><ForeName>Emmanuel</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>the Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada, Pfizer Canada Inc., Kirkland, Quebec H9J 2M5, Canada, and.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>González</LastName><ForeName>Jose L</ForeName><Initials>JL</Initials><AffiliationInfo><Affiliation>the Division of Basic Science, National Institute of Cancer, 22 San Fernando Ave., Tlalpan, Mexico City 14080, Mexico.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hernández</LastName><ForeName>Greco</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>the Division of Basic Science, National Institute of Cancer, 22 San Fernando Ave., Tlalpan, Mexico City 14080, Mexico.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Alain</LastName><ForeName>Tommy</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>From the Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8L1, Canada, tommy@arc.cheo.ca.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Damgaard</LastName><ForeName>Christian K</ForeName><Initials>CK</Initials><AffiliationInfo><Affiliation>the Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus C, Denmark, ckd@mbg.au.dk.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2015</Year><Month>05</Month><Day>04</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Biol Chem</MedlineTA><NlmUniqueID>2985121R</NlmUniqueID><ISSNLinking>0021-9258</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D048868">Adaptor Proteins, Signal Transducing</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D001324">Autoantigens</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D039561">Eukaryotic Initiation Factor-4E</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D008562">Membrane Glycoproteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D046912">Multiprotein Complexes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D012333">RNA, Messenger</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C463659">RPTOR protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000076223">Regulatory-Associated Protein of mTOR</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D012261">Ribonucleoproteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C035416">SS-B antigen</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C509980">TOP protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber><NameOfSubstance UI="D058570">TOR Serine-Threonine Kinases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="D000076222">Mechanistic Target of Rapamycin Complex 1</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D048868" MajorTopicYN="N">Adaptor Proteins, Signal Transducing</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001324" MajorTopicYN="N">Autoantigens</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015536" MajorTopicYN="Y">Down-Regulation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D039561" MajorTopicYN="N">Eukaryotic Initiation Factor-4E</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000076222" MajorTopicYN="N">Mechanistic Target of Rapamycin Complex 1</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008562" MajorTopicYN="N">Membrane Glycoproteins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D046912" MajorTopicYN="N">Multiprotein Complexes</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011485" MajorTopicYN="N">Protein Binding</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014176" MajorTopicYN="Y">Protein Biosynthesis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012333" MajorTopicYN="N">RNA, Messenger</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000076223" MajorTopicYN="N">Regulatory-Associated Protein of mTOR</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012261" MajorTopicYN="N">Ribonucleoproteins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D058570" MajorTopicYN="N">TOR Serine-Threonine Kinases</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">5'-terminal oligopyrimidine (5'TOP) motif</Keyword><Keyword MajorTopicYN="N">La-related protein 1 (LARP1)</Keyword><Keyword MajorTopicYN="N">TOP mRNA translation</Keyword><Keyword MajorTopicYN="N">gene expression</Keyword><Keyword MajorTopicYN="N">mTOR complex 1 (mTORC1)</Keyword><Keyword MajorTopicYN="N">mammalian target of rapamycin (mTOR)</Keyword><Keyword MajorTopicYN="N">protein synthesis</Keyword><Keyword MajorTopicYN="N">repressor protein</Keyword><Keyword MajorTopicYN="N">ribosome biogenesis</Keyword><Keyword MajorTopicYN="N">translation</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2014</Year><Month>11</Month><Day>04</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2015</Year><Month>5</Month><Day>6</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2015</Year><Month>5</Month><Day>6</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2015</Year><Month>10</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId 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IdType="pubmed">23105104</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></pubmed><affiliations><list><country><li>Canada</li><li>Danemark</li><li>Mexique</li><li>Oman</li><li>Royaume-Uni</li></country><region><li>Québec</li></region><settlement><li>Montréal</li></settlement><orgName><li>Université McGill</li></orgName></list><tree><country name="Oman"><noRegion><name sortKey="Fonseca, Bruno D" sort="Fonseca, Bruno D" uniqKey="Fonseca B" first="Bruno D" last="Fonseca">Bruno D. Fonseca</name></noRegion></country><country name="Canada"><region name="Québec"><name sortKey="Zakaria, Chadi" sort="Zakaria, Chadi" uniqKey="Zakaria C" first="Chadi" last="Zakaria">Chadi Zakaria</name></region><name sortKey="Alain, Tommy" sort="Alain, Tommy" uniqKey="Alain T" first="Tommy" last="Alain">Tommy Alain</name><name sortKey="Dajadian, Christopher" sort="Dajadian, Christopher" uniqKey="Dajadian C" first="Christopher" last="Dajadian">Christopher Dajadian</name><name sortKey="Graber, Tyson E" sort="Graber, Tyson E" uniqKey="Graber T" first="Tyson E" last="Graber">Tyson E. Graber</name><name sortKey="Healy, Danielle" sort="Healy, Danielle" uniqKey="Healy D" first="Danielle" last="Healy">Danielle Healy</name><name sortKey="Hearnden, Jaclyn" sort="Hearnden, Jaclyn" uniqKey="Hearnden J" first="Jaclyn" last="Hearnden">Jaclyn Hearnden</name><name sortKey="Hoang, Huy Dung" sort="Hoang, Huy Dung" uniqKey="Hoang H" first="Huy-Dung" last="Hoang">Huy-Dung Hoang</name><name sortKey="Jia, Jian Jun" sort="Jia, Jian Jun" uniqKey="Jia J" first="Jian-Jun" last="Jia">Jian-Jun Jia</name><name sortKey="Lussier, Alexandre" sort="Lussier, Alexandre" uniqKey="Lussier A" first="Alexandre" last="Lussier">Alexandre Lussier</name><name sortKey="Matta Camacho, Edna" sort="Matta Camacho, Edna" uniqKey="Matta Camacho E" first="Edna" last="Matta-Camacho">Edna Matta-Camacho</name><name sortKey="Morita, Masahiro" sort="Morita, Masahiro" uniqKey="Morita M" first="Masahiro" last="Morita">Masahiro Morita</name><name sortKey="Padmanabhan, Niranjan" sort="Padmanabhan, Niranjan" uniqKey="Padmanabhan N" first="Niranjan" last="Padmanabhan">Niranjan Padmanabhan</name><name sortKey="Petroulakis, Emmanuel" sort="Petroulakis, Emmanuel" uniqKey="Petroulakis E" first="Emmanuel" last="Petroulakis">Emmanuel Petroulakis</name><name sortKey="Svitkin, Yuri" sort="Svitkin, Yuri" uniqKey="Svitkin Y" first="Yuri" last="Svitkin">Yuri Svitkin</name><name sortKey="Tahmasebi, Soroush" sort="Tahmasebi, Soroush" uniqKey="Tahmasebi S" first="Soroush" last="Tahmasebi">Soroush Tahmasebi</name><name sortKey="Tsukumo, Yoshinori" sort="Tsukumo, Yoshinori" uniqKey="Tsukumo Y" first="Yoshinori" last="Tsukumo">Yoshinori Tsukumo</name><name sortKey="Wang, Walter" sort="Wang, Walter" uniqKey="Wang W" first="Walter" last="Wang">Walter Wang</name><name sortKey="Yanagiya, Akiko" sort="Yanagiya, Akiko" uniqKey="Yanagiya A" first="Akiko" last="Yanagiya">Akiko Yanagiya</name></country><country name="Danemark"><noRegion><name sortKey="Jensen, Jacob M" sort="Jensen, Jacob M" uniqKey="Jensen J" first="Jacob M" last="Jensen">Jacob M. Jensen</name></noRegion><name sortKey="Damgaard, Christian K" sort="Damgaard, Christian K" uniqKey="Damgaard C" first="Christian K" last="Damgaard">Christian K. Damgaard</name><name sortKey="Diao, Ilo T" sort="Diao, Ilo T" uniqKey="Diao I" first="Ilo T" last="Diao">Ilo T. Diao</name></country><country name="Royaume-Uni"><noRegion><name sortKey="Smith, Ewan M" sort="Smith, Ewan M" uniqKey="Smith E" first="Ewan M" last="Smith">Ewan M. Smith</name></noRegion></country><country name="Mexique"><noRegion><name sortKey="Gonzalez, Jose L" sort="Gonzalez, Jose L" uniqKey="Gonzalez J" first="Jose L" last="González">Jose L. González</name></noRegion><name sortKey="Hernandez, Greco" sort="Hernandez, Greco" uniqKey="Hernandez G" first="Greco" last="Hernández">Greco Hernández</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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