The helicase Ded1p controls use of near-cognate translation initiation codons in 5′UTRs View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-06-27

AUTHORS

Ulf-Peter Guenther, David E. Weinberg, Meghan M. Zubradt, Frank A. Tedeschi, Brittany N. Stawicki, Leah L. Zagore, Gloria A. Brar, Donny D. Licatalosi, David P. Bartel, Jonathan S. Weissman, Eckhard Jankowsky

ABSTRACT

The conserved and essential DEAD-box RNA helicase Ded1p from yeast and its mammalian orthologue DDX3 are critical for the initiation of translation1. Mutations in DDX3 are linked to tumorigenesis2-4 and intellectual disability5, and the enzyme is targeted by a range of viruses6. How Ded1p and its orthologues engage RNAs during the initiation of translation is unknown. Here we show, by integrating transcriptome-wide analyses of translation, RNA structure and Ded1p-RNA binding, that the effects of Ded1p on the initiation of translation are connected to near-cognate initiation codons in 5' untranslated regions. Ded1p associates with the translation pre-initiation complex at the mRNA entry channel and repressing the activity of Ded1p leads to the accumulation of RNA structure in 5' untranslated regions, the initiation of translation from near-cognate start codons immediately upstream of these structures and decreased protein synthesis from the corresponding main open reading frames. The data reveal a program for the regulation of translation that links Ded1p, the activation of near-cognate start codons and mRNA structure. This program has a role in meiosis, in which a marked decrease in the levels of Ded1p is accompanied by the activation of the alternative translation initiation sites that are seen when the activity of Ded1p is repressed. Our observations indicate that Ded1p affects translation initiation by controlling the use of near-cognate initiation codons that are proximal to mRNA structure in 5' untranslated regions. More... »

PAGES

130-134

References to SciGraph publications

  • 2015-11-05. DDX3, a potential target for cancer treatment in MOLECULAR CANCER
  • 2009-02-03. GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists in BMC BIOINFORMATICS
  • 2016-11-07. DMS-MaPseq for genome-wide or targeted RNA structure probing in vivo in NATURE METHODS
  • 2005-01-30. Exploring functional relationships between components of the gene expression machinery in NATURE STRUCTURAL & MOLECULAR BIOLOGY
  • 2014-01-29. Poly(A)-tail profiling reveals an embryonic switch in translational control in NATURE
  • 2015-02-09. Structure of a Yeast 40S–eIF1–eIF1A–eIF3–eIF3j initiation complex in NATURE STRUCTURAL & MOLECULAR BIOLOGY
  • 2014-02-11. Emerging evidence for functional peptides encoded by short open reading frames in NATURE REVIEWS GENETICS
  • 2008-11-02. HITS-CLIP yields genome-wide insights into brain alternative RNA processing in NATURE
  • 2014-12-18. The ViennaRNA Web Services in RNA BIOINFORMATICS
  • 2012-07-22. MEDULLOBLASTOMA EXOME SEQUENCING UNCOVERS SUBTYPE-SPECIFIC SOMATIC MUTATIONS in NATURE
  • 2012-07-26. The ribosome profiling strategy for monitoring translation in vivo by deep sequencing of ribosome-protected mRNA fragments in NATURE PROTOCOLS
  • 2010-08-25. Galaxy: a comprehensive approach for supporting accessible, reproducible, and transparent computational research in the life sciences in GENOME BIOLOGY
  • 2011-01-01. Integrative Genomics Viewer in NATURE BIOTECHNOLOGY
  • 2010-07-04. iCLIP reveals the function of hnRNP particles in splicing at individual nucleotide resolution in NATURE STRUCTURAL & MOLECULAR BIOLOGY
  • 2006-01-22. Proteome survey reveals modularity of the yeast cell machinery in NATURE
  • 2009-08-23. Co-translational mRNA decay in Saccharomyces cerevisiae in NATURE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41586-018-0258-0

    DOI

    http://dx.doi.org/10.1038/s41586-018-0258-0

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1105150810

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29950728


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Biological Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0604", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Genetics", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "5' Untranslated Regions", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Codon, Initiator", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cross-Linking Reagents", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "DEAD-box RNA Helicases", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Peptide Chain Initiation, Translational", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Ribosome Subunits, Small, Eukaryotic", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Saccharomyces cerevisiae", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Saccharomyces cerevisiae Proteins", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Center for RNA Science and Therapeutics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA", 
              "id": "http://www.grid.ac/institutes/grid.67105.35", 
              "name": [
                "Center for RNA Science and Therapeutics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Guenther", 
            "givenName": "Ulf-Peter", 
            "id": "sg:person.01207165513.45", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01207165513.45"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Howard Hughes Medical Institute; Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139", 
              "id": "http://www.grid.ac/institutes/grid.270301.7", 
              "name": [
                "Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA", 
                "Howard Hughes Medical Institute; Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Weinberg", 
            "givenName": "David E.", 
            "id": "sg:person.0662260226.07", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0662260226.07"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Howard Hughes Medical Institute and California Institute for Quantitative Biomedical Research, San Francisco, CA 94158, USA", 
              "id": "http://www.grid.ac/institutes/None", 
              "name": [
                "Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA", 
                "Howard Hughes Medical Institute and California Institute for Quantitative Biomedical Research, San Francisco, CA 94158, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Zubradt", 
            "givenName": "Meghan M.", 
            "id": "sg:person.0675120262.60", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0675120262.60"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Center for RNA Science and Therapeutics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA", 
              "id": "http://www.grid.ac/institutes/grid.67105.35", 
              "name": [
                "Center for RNA Science and Therapeutics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Tedeschi", 
            "givenName": "Frank A.", 
            "id": "sg:person.010251635734.98", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010251635734.98"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Center for RNA Science and Therapeutics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA", 
              "id": "http://www.grid.ac/institutes/grid.67105.35", 
              "name": [
                "Center for RNA Science and Therapeutics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Stawicki", 
            "givenName": "Brittany N.", 
            "id": "sg:person.011662112257.91", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011662112257.91"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Center for RNA Science and Therapeutics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA", 
              "id": "http://www.grid.ac/institutes/grid.67105.35", 
              "name": [
                "Center for RNA Science and Therapeutics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Zagore", 
            "givenName": "Leah L.", 
            "id": "sg:person.01334507165.67", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01334507165.67"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA", 
              "id": "http://www.grid.ac/institutes/grid.47840.3f", 
              "name": [
                "Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Brar", 
            "givenName": "Gloria A.", 
            "id": "sg:person.01350124511.60", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01350124511.60"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Center for RNA Science and Therapeutics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA", 
              "id": "http://www.grid.ac/institutes/grid.67105.35", 
              "name": [
                "Center for RNA Science and Therapeutics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Licatalosi", 
            "givenName": "Donny D.", 
            "id": "sg:person.01035626451.71", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01035626451.71"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Howard Hughes Medical Institute; Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139", 
              "id": "http://www.grid.ac/institutes/grid.270301.7", 
              "name": [
                "Howard Hughes Medical Institute; Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Bartel", 
            "givenName": "David P.", 
            "id": "sg:person.01331434117.61", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01331434117.61"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Howard Hughes Medical Institute and California Institute for Quantitative Biomedical Research, San Francisco, CA 94158, USA", 
              "id": "http://www.grid.ac/institutes/None", 
              "name": [
                "Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA", 
                "Howard Hughes Medical Institute and California Institute for Quantitative Biomedical Research, San Francisco, CA 94158, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Weissman", 
            "givenName": "Jonathan S.", 
            "id": "sg:person.01143024036.14", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01143024036.14"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Physics, Case Western Reserve University, Cleveland, OH 44106, USA", 
              "id": "http://www.grid.ac/institutes/grid.67105.35", 
              "name": [
                "Center for RNA Science and Therapeutics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA", 
                "Department of Physics, Case Western Reserve University, Cleveland, OH 44106, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Jankowsky", 
            "givenName": "Eckhard", 
            "id": "sg:person.01367224716.02", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01367224716.02"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1038/nrg3520", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1018701184", 
              "https://doi.org/10.1038/nrg3520"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature11329", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1036872856", 
              "https://doi.org/10.1038/nature11329"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/978-1-4939-2291-8_19", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021292362", 
              "https://doi.org/10.1007/978-1-4939-2291-8_19"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nbt.1754", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1019307928", 
              "https://doi.org/10.1038/nbt.1754"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s12943-015-0461-7", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1051439360", 
              "https://doi.org/10.1186/s12943-015-0461-7"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature08265", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1004008241", 
              "https://doi.org/10.1038/nature08265"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/1471-2105-10-48", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1048544728", 
              "https://doi.org/10.1186/1471-2105-10-48"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nsmb.1838", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1009634080", 
              "https://doi.org/10.1038/nsmb.1838"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/gb-2010-11-8-r86", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1046347776", 
              "https://doi.org/10.1186/gb-2010-11-8-r86"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nprot.2012.086", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010450110", 
              "https://doi.org/10.1038/nprot.2012.086"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nsmb891", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1027221069", 
              "https://doi.org/10.1038/nsmb891"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature04532", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1043981355", 
              "https://doi.org/10.1038/nature04532"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature13007", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1039828985", 
              "https://doi.org/10.1038/nature13007"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature07488", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010813801", 
              "https://doi.org/10.1038/nature07488"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nmeth.4057", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1039409810", 
              "https://doi.org/10.1038/nmeth.4057"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nsmb.2963", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1053632305", 
              "https://doi.org/10.1038/nsmb.2963"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2018-06-27", 
        "datePublishedReg": "2018-06-27", 
        "description": "The conserved and essential DEAD-box RNA helicase Ded1p from yeast and its mammalian orthologue DDX3 are critical for the initiation of translation1. Mutations in DDX3 are linked to tumorigenesis2-4 and intellectual disability5, and the enzyme is targeted by a range of viruses6. How Ded1p and its orthologues engage RNAs during the initiation of translation is unknown. Here we show, by integrating transcriptome-wide analyses of translation, RNA structure and Ded1p-RNA binding, that the effects of Ded1p on the initiation of translation are connected to near-cognate initiation codons in 5' untranslated regions. Ded1p associates with the translation pre-initiation complex at the mRNA entry channel and repressing the activity of Ded1p leads to the accumulation of RNA structure in 5' untranslated regions, the initiation of translation from near-cognate start codons immediately upstream of these structures and decreased protein synthesis from the corresponding main open reading frames. The data reveal a program for the regulation of translation that links Ded1p, the activation of near-cognate start codons and mRNA structure. This program has a role in meiosis, in which a marked decrease in the levels of Ded1p is accompanied by the activation of the alternative translation initiation sites that are seen when the activity of Ded1p is repressed. Our observations indicate that Ded1p affects translation initiation by controlling the use of near-cognate initiation codons that are proximal to mRNA structure in 5' untranslated regions.", 
        "genre": "article", 
        "id": "sg:pub.10.1038/s41586-018-0258-0", 
        "inLanguage": "en", 
        "isAccessibleForFree": true, 
        "isFundedItemOf": [
          {
            "id": "sg:grant.5124436", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.2683845", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.5053649", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.2522112", 
            "type": "MonetaryGrant"
          }
        ], 
        "isPartOf": [
          {
            "id": "sg:journal.1018957", 
            "issn": [
              "0028-0836", 
              "1476-4687"
            ], 
            "name": "Nature", 
            "publisher": "Springer Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "7712", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "559"
          }
        ], 
        "keywords": [
          "initiation of translation", 
          "cognate start codons", 
          "initiation codon", 
          "untranslated region", 
          "mRNA structure", 
          "start codon", 
          "RNA structure", 
          "translation pre-initiation complex", 
          "alternative translation initiation sites", 
          "mRNA entry channel", 
          "transcriptome-wide analysis", 
          "pre-initiation complex", 
          "regulation of translation", 
          "main open reading frame", 
          "open reading frame", 
          "translation initiation codon", 
          "translation initiation site", 
          "translation initiation", 
          "Ded1p", 
          "reading frame", 
          "initiation site", 
          "codon", 
          "protein synthesis", 
          "entry channels", 
          "range of viruses", 
          "DDX3", 
          "translation", 
          "orthologues", 
          "meiosis", 
          "activation", 
          "yeast", 
          "RNA", 
          "initiation", 
          "mutations", 
          "enzyme", 
          "regulation", 
          "region", 
          "binding", 
          "associates", 
          "activity", 
          "accumulation", 
          "complexes", 
          "intellectual disability", 
          "structure", 
          "sites", 
          "virus", 
          "role", 
          "synthesis", 
          "frame", 
          "levels", 
          "analysis", 
          "channels", 
          "decrease", 
          "effect", 
          "observations", 
          "data", 
          "range", 
          "program", 
          "use", 
          "disability", 
          "essential DEAD-box RNA helicase Ded1p", 
          "DEAD-box RNA helicase Ded1p", 
          "RNA helicase Ded1p", 
          "helicase Ded1p", 
          "mammalian orthologue DDX3", 
          "orthologue DDX3", 
          "Ded1p-RNA binding", 
          "effects of Ded1p", 
          "cognate initiation codons", 
          "Ded1p associates", 
          "activity of Ded1p", 
          "levels of Ded1p", 
          "near-cognate initiation codons", 
          "near-cognate translation initiation codons"
        ], 
        "name": "The helicase Ded1p controls use of near-cognate translation initiation codons in 5\u2032UTRs", 
        "pagination": "130-134", 
        "productId": [
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1105150810"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/s41586-018-0258-0"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "29950728"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/s41586-018-0258-0", 
          "https://app.dimensions.ai/details/publication/pub.1105150810"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2022-01-01T18:49", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20220101/entities/gbq_results/article/article_780.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://doi.org/10.1038/s41586-018-0258-0"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41586-018-0258-0'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41586-018-0258-0'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41586-018-0258-0'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41586-018-0258-0'


     

    This table displays all metadata directly associated to this object as RDF triples.

    323 TRIPLES      22 PREDICATES      124 URIs      100 LITERALS      15 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/s41586-018-0258-0 schema:about N42d028dbf4f946edb77979fef75e8813
    2 N476c8050ad484d8a9c8341d3edb47807
    3 N79c1ed43448d4fa4aed184e68c9ac1eb
    4 N820f566db6cf4c4ea69388216e01af7e
    5 N9a65a1549aa14878b52a88aad1e0b150
    6 N9b36fec3f7d74f69b89b50dde493668e
    7 Na97aca1413144ac5bd4f709a0119f81e
    8 Nf7899b28ad854d93b9ae118c476e4476
    9 anzsrc-for:06
    10 anzsrc-for:0604
    11 schema:author N7dd787ffb02f4471a29060bad091957e
    12 schema:citation sg:pub.10.1007/978-1-4939-2291-8_19
    13 sg:pub.10.1038/nature04532
    14 sg:pub.10.1038/nature07488
    15 sg:pub.10.1038/nature08265
    16 sg:pub.10.1038/nature11329
    17 sg:pub.10.1038/nature13007
    18 sg:pub.10.1038/nbt.1754
    19 sg:pub.10.1038/nmeth.4057
    20 sg:pub.10.1038/nprot.2012.086
    21 sg:pub.10.1038/nrg3520
    22 sg:pub.10.1038/nsmb.1838
    23 sg:pub.10.1038/nsmb.2963
    24 sg:pub.10.1038/nsmb891
    25 sg:pub.10.1186/1471-2105-10-48
    26 sg:pub.10.1186/gb-2010-11-8-r86
    27 sg:pub.10.1186/s12943-015-0461-7
    28 schema:datePublished 2018-06-27
    29 schema:datePublishedReg 2018-06-27
    30 schema:description The conserved and essential DEAD-box RNA helicase Ded1p from yeast and its mammalian orthologue DDX3 are critical for the initiation of translation<sup>1</sup>. Mutations in DDX3 are linked to tumorigenesis<sup>2-4</sup> and intellectual disability<sup>5</sup>, and the enzyme is targeted by a range of viruses<sup>6</sup>. How Ded1p and its orthologues engage RNAs during the initiation of translation is unknown. Here we show, by integrating transcriptome-wide analyses of translation, RNA structure and Ded1p-RNA binding, that the effects of Ded1p on the initiation of translation are connected to near-cognate initiation codons in 5' untranslated regions. Ded1p associates with the translation pre-initiation complex at the mRNA entry channel and repressing the activity of Ded1p leads to the accumulation of RNA structure in 5' untranslated regions, the initiation of translation from near-cognate start codons immediately upstream of these structures and decreased protein synthesis from the corresponding main open reading frames. The data reveal a program for the regulation of translation that links Ded1p, the activation of near-cognate start codons and mRNA structure. This program has a role in meiosis, in which a marked decrease in the levels of Ded1p is accompanied by the activation of the alternative translation initiation sites that are seen when the activity of Ded1p is repressed. Our observations indicate that Ded1p affects translation initiation by controlling the use of near-cognate initiation codons that are proximal to mRNA structure in 5' untranslated regions.
    31 schema:genre article
    32 schema:inLanguage en
    33 schema:isAccessibleForFree true
    34 schema:isPartOf N2a3422bda6904eeb84a543fd954b2958
    35 Nbe46e1c3fecb48dbb9ad27b08bb31d80
    36 sg:journal.1018957
    37 schema:keywords DDX3
    38 DEAD-box RNA helicase Ded1p
    39 Ded1p
    40 Ded1p associates
    41 Ded1p-RNA binding
    42 RNA
    43 RNA helicase Ded1p
    44 RNA structure
    45 accumulation
    46 activation
    47 activity
    48 activity of Ded1p
    49 alternative translation initiation sites
    50 analysis
    51 associates
    52 binding
    53 channels
    54 codon
    55 cognate initiation codons
    56 cognate start codons
    57 complexes
    58 data
    59 decrease
    60 disability
    61 effect
    62 effects of Ded1p
    63 entry channels
    64 enzyme
    65 essential DEAD-box RNA helicase Ded1p
    66 frame
    67 helicase Ded1p
    68 initiation
    69 initiation codon
    70 initiation of translation
    71 initiation site
    72 intellectual disability
    73 levels
    74 levels of Ded1p
    75 mRNA entry channel
    76 mRNA structure
    77 main open reading frame
    78 mammalian orthologue DDX3
    79 meiosis
    80 mutations
    81 near-cognate initiation codons
    82 near-cognate translation initiation codons
    83 observations
    84 open reading frame
    85 orthologue DDX3
    86 orthologues
    87 pre-initiation complex
    88 program
    89 protein synthesis
    90 range
    91 range of viruses
    92 reading frame
    93 region
    94 regulation
    95 regulation of translation
    96 role
    97 sites
    98 start codon
    99 structure
    100 synthesis
    101 transcriptome-wide analysis
    102 translation
    103 translation initiation
    104 translation initiation codon
    105 translation initiation site
    106 translation pre-initiation complex
    107 untranslated region
    108 use
    109 virus
    110 yeast
    111 schema:name The helicase Ded1p controls use of near-cognate translation initiation codons in 5′UTRs
    112 schema:pagination 130-134
    113 schema:productId N4dbef514e4b1448e8fbf7c61ea5381d5
    114 N8f559cb187a4426e99106dd38828c8ee
    115 Nf399d80fca38418c9c08adcfa0596f71
    116 schema:sameAs https://app.dimensions.ai/details/publication/pub.1105150810
    117 https://doi.org/10.1038/s41586-018-0258-0
    118 schema:sdDatePublished 2022-01-01T18:49
    119 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    120 schema:sdPublisher Nd5c8441fc45040d09bcc0c66c0a55dac
    121 schema:url https://doi.org/10.1038/s41586-018-0258-0
    122 sgo:license sg:explorer/license/
    123 sgo:sdDataset articles
    124 rdf:type schema:ScholarlyArticle
    125 N2a3422bda6904eeb84a543fd954b2958 schema:issueNumber 7712
    126 rdf:type schema:PublicationIssue
    127 N2a68d75f11da4bd49b2bca00e25b1ebf rdf:first sg:person.0662260226.07
    128 rdf:rest Ne2ba1273ad704dc89cd278cb475c7318
    129 N2e163cbd8e0d47bb816063a6d73920b5 rdf:first sg:person.01331434117.61
    130 rdf:rest N515da7280dd34a568e3348c9be0d56c1
    131 N42d028dbf4f946edb77979fef75e8813 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    132 schema:name Codon, Initiator
    133 rdf:type schema:DefinedTerm
    134 N435cf05863764abb8de84cb0749d4deb rdf:first sg:person.011662112257.91
    135 rdf:rest N6219cf691ccd485290d6f4d46df3c12e
    136 N476c8050ad484d8a9c8341d3edb47807 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    137 schema:name Saccharomyces cerevisiae Proteins
    138 rdf:type schema:DefinedTerm
    139 N4dbef514e4b1448e8fbf7c61ea5381d5 schema:name dimensions_id
    140 schema:value pub.1105150810
    141 rdf:type schema:PropertyValue
    142 N515da7280dd34a568e3348c9be0d56c1 rdf:first sg:person.01143024036.14
    143 rdf:rest Nca8a31c614bd4b2099859c29227382d2
    144 N6219cf691ccd485290d6f4d46df3c12e rdf:first sg:person.01334507165.67
    145 rdf:rest N7058e22b08d044e0bcbaef58b8257359
    146 N7058e22b08d044e0bcbaef58b8257359 rdf:first sg:person.01350124511.60
    147 rdf:rest Nd4251a7d6aa84462805cfd1df3e81a28
    148 N79c1ed43448d4fa4aed184e68c9ac1eb schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    149 schema:name DEAD-box RNA Helicases
    150 rdf:type schema:DefinedTerm
    151 N7dd787ffb02f4471a29060bad091957e rdf:first sg:person.01207165513.45
    152 rdf:rest N2a68d75f11da4bd49b2bca00e25b1ebf
    153 N820f566db6cf4c4ea69388216e01af7e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    154 schema:name Saccharomyces cerevisiae
    155 rdf:type schema:DefinedTerm
    156 N8f559cb187a4426e99106dd38828c8ee schema:name doi
    157 schema:value 10.1038/s41586-018-0258-0
    158 rdf:type schema:PropertyValue
    159 N9a65a1549aa14878b52a88aad1e0b150 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    160 schema:name Cross-Linking Reagents
    161 rdf:type schema:DefinedTerm
    162 N9b36fec3f7d74f69b89b50dde493668e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    163 schema:name 5' Untranslated Regions
    164 rdf:type schema:DefinedTerm
    165 Na97aca1413144ac5bd4f709a0119f81e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    166 schema:name Ribosome Subunits, Small, Eukaryotic
    167 rdf:type schema:DefinedTerm
    168 Nbe46e1c3fecb48dbb9ad27b08bb31d80 schema:volumeNumber 559
    169 rdf:type schema:PublicationVolume
    170 Nca8a31c614bd4b2099859c29227382d2 rdf:first sg:person.01367224716.02
    171 rdf:rest rdf:nil
    172 Nd1ef8c8928574cb088b39bf1b725b82e rdf:first sg:person.010251635734.98
    173 rdf:rest N435cf05863764abb8de84cb0749d4deb
    174 Nd4251a7d6aa84462805cfd1df3e81a28 rdf:first sg:person.01035626451.71
    175 rdf:rest N2e163cbd8e0d47bb816063a6d73920b5
    176 Nd5c8441fc45040d09bcc0c66c0a55dac schema:name Springer Nature - SN SciGraph project
    177 rdf:type schema:Organization
    178 Ne2ba1273ad704dc89cd278cb475c7318 rdf:first sg:person.0675120262.60
    179 rdf:rest Nd1ef8c8928574cb088b39bf1b725b82e
    180 Nf399d80fca38418c9c08adcfa0596f71 schema:name pubmed_id
    181 schema:value 29950728
    182 rdf:type schema:PropertyValue
    183 Nf7899b28ad854d93b9ae118c476e4476 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    184 schema:name Peptide Chain Initiation, Translational
    185 rdf:type schema:DefinedTerm
    186 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
    187 schema:name Biological Sciences
    188 rdf:type schema:DefinedTerm
    189 anzsrc-for:0604 schema:inDefinedTermSet anzsrc-for:
    190 schema:name Genetics
    191 rdf:type schema:DefinedTerm
    192 sg:grant.2522112 http://pending.schema.org/fundedItem sg:pub.10.1038/s41586-018-0258-0
    193 rdf:type schema:MonetaryGrant
    194 sg:grant.2683845 http://pending.schema.org/fundedItem sg:pub.10.1038/s41586-018-0258-0
    195 rdf:type schema:MonetaryGrant
    196 sg:grant.5053649 http://pending.schema.org/fundedItem sg:pub.10.1038/s41586-018-0258-0
    197 rdf:type schema:MonetaryGrant
    198 sg:grant.5124436 http://pending.schema.org/fundedItem sg:pub.10.1038/s41586-018-0258-0
    199 rdf:type schema:MonetaryGrant
    200 sg:journal.1018957 schema:issn 0028-0836
    201 1476-4687
    202 schema:name Nature
    203 schema:publisher Springer Nature
    204 rdf:type schema:Periodical
    205 sg:person.010251635734.98 schema:affiliation grid-institutes:grid.67105.35
    206 schema:familyName Tedeschi
    207 schema:givenName Frank A.
    208 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010251635734.98
    209 rdf:type schema:Person
    210 sg:person.01035626451.71 schema:affiliation grid-institutes:grid.67105.35
    211 schema:familyName Licatalosi
    212 schema:givenName Donny D.
    213 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01035626451.71
    214 rdf:type schema:Person
    215 sg:person.01143024036.14 schema:affiliation grid-institutes:None
    216 schema:familyName Weissman
    217 schema:givenName Jonathan S.
    218 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01143024036.14
    219 rdf:type schema:Person
    220 sg:person.011662112257.91 schema:affiliation grid-institutes:grid.67105.35
    221 schema:familyName Stawicki
    222 schema:givenName Brittany N.
    223 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011662112257.91
    224 rdf:type schema:Person
    225 sg:person.01207165513.45 schema:affiliation grid-institutes:grid.67105.35
    226 schema:familyName Guenther
    227 schema:givenName Ulf-Peter
    228 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01207165513.45
    229 rdf:type schema:Person
    230 sg:person.01331434117.61 schema:affiliation grid-institutes:grid.270301.7
    231 schema:familyName Bartel
    232 schema:givenName David P.
    233 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01331434117.61
    234 rdf:type schema:Person
    235 sg:person.01334507165.67 schema:affiliation grid-institutes:grid.67105.35
    236 schema:familyName Zagore
    237 schema:givenName Leah L.
    238 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01334507165.67
    239 rdf:type schema:Person
    240 sg:person.01350124511.60 schema:affiliation grid-institutes:grid.47840.3f
    241 schema:familyName Brar
    242 schema:givenName Gloria A.
    243 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01350124511.60
    244 rdf:type schema:Person
    245 sg:person.01367224716.02 schema:affiliation grid-institutes:grid.67105.35
    246 schema:familyName Jankowsky
    247 schema:givenName Eckhard
    248 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01367224716.02
    249 rdf:type schema:Person
    250 sg:person.0662260226.07 schema:affiliation grid-institutes:grid.270301.7
    251 schema:familyName Weinberg
    252 schema:givenName David E.
    253 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0662260226.07
    254 rdf:type schema:Person
    255 sg:person.0675120262.60 schema:affiliation grid-institutes:None
    256 schema:familyName Zubradt
    257 schema:givenName Meghan M.
    258 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0675120262.60
    259 rdf:type schema:Person
    260 sg:pub.10.1007/978-1-4939-2291-8_19 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021292362
    261 https://doi.org/10.1007/978-1-4939-2291-8_19
    262 rdf:type schema:CreativeWork
    263 sg:pub.10.1038/nature04532 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043981355
    264 https://doi.org/10.1038/nature04532
    265 rdf:type schema:CreativeWork
    266 sg:pub.10.1038/nature07488 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010813801
    267 https://doi.org/10.1038/nature07488
    268 rdf:type schema:CreativeWork
    269 sg:pub.10.1038/nature08265 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004008241
    270 https://doi.org/10.1038/nature08265
    271 rdf:type schema:CreativeWork
    272 sg:pub.10.1038/nature11329 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036872856
    273 https://doi.org/10.1038/nature11329
    274 rdf:type schema:CreativeWork
    275 sg:pub.10.1038/nature13007 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039828985
    276 https://doi.org/10.1038/nature13007
    277 rdf:type schema:CreativeWork
    278 sg:pub.10.1038/nbt.1754 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019307928
    279 https://doi.org/10.1038/nbt.1754
    280 rdf:type schema:CreativeWork
    281 sg:pub.10.1038/nmeth.4057 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039409810
    282 https://doi.org/10.1038/nmeth.4057
    283 rdf:type schema:CreativeWork
    284 sg:pub.10.1038/nprot.2012.086 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010450110
    285 https://doi.org/10.1038/nprot.2012.086
    286 rdf:type schema:CreativeWork
    287 sg:pub.10.1038/nrg3520 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018701184
    288 https://doi.org/10.1038/nrg3520
    289 rdf:type schema:CreativeWork
    290 sg:pub.10.1038/nsmb.1838 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009634080
    291 https://doi.org/10.1038/nsmb.1838
    292 rdf:type schema:CreativeWork
    293 sg:pub.10.1038/nsmb.2963 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053632305
    294 https://doi.org/10.1038/nsmb.2963
    295 rdf:type schema:CreativeWork
    296 sg:pub.10.1038/nsmb891 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027221069
    297 https://doi.org/10.1038/nsmb891
    298 rdf:type schema:CreativeWork
    299 sg:pub.10.1186/1471-2105-10-48 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048544728
    300 https://doi.org/10.1186/1471-2105-10-48
    301 rdf:type schema:CreativeWork
    302 sg:pub.10.1186/gb-2010-11-8-r86 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046347776
    303 https://doi.org/10.1186/gb-2010-11-8-r86
    304 rdf:type schema:CreativeWork
    305 sg:pub.10.1186/s12943-015-0461-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051439360
    306 https://doi.org/10.1186/s12943-015-0461-7
    307 rdf:type schema:CreativeWork
    308 grid-institutes:None schema:alternateName Howard Hughes Medical Institute and California Institute for Quantitative Biomedical Research, San Francisco, CA 94158, USA
    309 schema:name Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA
    310 Howard Hughes Medical Institute and California Institute for Quantitative Biomedical Research, San Francisco, CA 94158, USA
    311 rdf:type schema:Organization
    312 grid-institutes:grid.270301.7 schema:alternateName Howard Hughes Medical Institute; Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139
    313 schema:name Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA
    314 Howard Hughes Medical Institute; Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139
    315 rdf:type schema:Organization
    316 grid-institutes:grid.47840.3f schema:alternateName Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
    317 schema:name Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
    318 rdf:type schema:Organization
    319 grid-institutes:grid.67105.35 schema:alternateName Center for RNA Science and Therapeutics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
    320 Department of Physics, Case Western Reserve University, Cleveland, OH 44106, USA
    321 schema:name Center for RNA Science and Therapeutics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
    322 Department of Physics, Case Western Reserve University, Cleveland, OH 44106, USA
    323 rdf:type schema:Organization
     




    Preview window. Press ESC to close (or click here)


    ...