The protein Sex-lethal antagonizes the splicing factor U2AF to regulate alternative splicing of transformer pre-mRNA View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1993-03

AUTHORS

J Valcárcel, R Singh, P D Zamore, M R Green

ABSTRACT

Somatic sexual differentiation in Drosophila melanogaster involves a cascade of regulated splicing events and provides an attractive model system for the analysis of alternative splicing mechanisms. The protein Sex-lethal (Sxl) activates a female-specific 3' splice site in the first intron of transformer (tra) pre-mRNA while repressing an alternative non-sex-specific site. We have developed an in vitro system that recapitulates this regulation in a manner consistent with genetic, transfection and fly transformation studies. Using this system, we have determined the molecular basis of the splice site switch. Here we show that Sxl inhibits splicing to the non-sex-specific (default) site by specifically binding to its polypyrimidine tract, blocking the binding of the essential splicing factor U2AF. This enables U2AF to activate the lower-affinity female-specific site. A splicing 'effector' domain present in U2AF but absent from Sxl accounts for the different activities of these two polypyrimidine-tract-binding proteins: addition of the U2AF effector domain to Sxl converts it from a splicing repressor to an activator and renders it unable to mediate splice-site switching. More... »

PAGES

171-175

Journal

TITLE

Nature

ISSUE

6416

VOLUME

362

Author Affiliations

Related Patents

  • Modified Polynucleotides For The Production Of Secreted Proteins
  • Engineered Nucleic Acids Encoding A Modified Erythropoietin And Their Expression
  • Modified Polynucleotides For The Production Of Biologics And Proteins Associated With Human Disease
  • Modified Polynucleotides For Treating Galactosylceramidase Protein Deficiency
  • Modified Polynucleotides Encoding Granulysin
  • Modified Polynucleotides Encoding Apoptosis Inducing Factor 1
  • Modified Polynucleotides For The Production Of Nuclear Proteins
  • Modified Polynucleotides Encoding Cited4
  • Modified Polynucleotides Encoding Septin-4
  • Engineered Nucleic Acids And Methods Of Use Thereof
  • Modified Nucleosides, Nucleotides, And Nucleic Acids, And Uses Thereof
  • Modified Polynucleotides For Treating Protein Deficiency
  • Delivery And Formulation Of Engineered Nucleic Acids
  • Modified Polynucleotides For The Production Of Proteins Associated With Human Disease
  • Delivery And Formulation Of Engineered Nucleic Acids
  • Engineered Nucleic Acids And Methods Of Use Thereof
  • Modified Polynucleotides Encoding Copper Metabolism (Murr1) Domain Containing 1
  • Artificial Riboswitch For Controlling Pre-Mrna Splicing
  • Engineered Nucleic Acids And Methods Of Use Thereof
  • Formulation And Delivery Of Plga Microspheres
  • Compositions And Methods Of Altering Cholesterol Levels
  • Modified Polynucleotides Encoding Basic Helix-Loop-Helix Family Member E41
  • Engineered Nucleic Acids And Methods Of Use Thereof
  • Engineered Nucleic Acids And Methods Of Use Thereof
  • Modified Polynucleotides For The Production Of Oncology-Related Proteins And Peptides
  • Modified Polynucleotides For The Production Of G-Csf
  • Engineered Nucleic Acids And Methods Of Use Thereof
  • Terminally Modified Rna
  • Modified Nucleosides, Nucleotides, And Nucleic Acids, And Uses Thereof
  • Engineered Nucleic Acids And Methods Of Use Thereof
  • Modified Polynucleotides For The Production Of Cosmetic Proteins And Peptides
  • Modified Polynucleotides Encoding Siah E3 Ubiquitin Protein Ligase 1
  • Dlin-Kc2-Dma Lipid Nanoparticle Delivery Of Modified Polynucleotides
  • Modified Polynucleotides For The Production Of Secreted Proteins
  • Modified Polynucleotides Encoding Hepatitis A Virus Cellular Receptor 2
  • In Vivo Production Of Proteins
  • Modified Polynucleotides For The Production Of Proteins
  • Modified Nucleosides, Nucleotides, And Nucleic Acids, And Uses Thereof
  • Method For Producing A Protein Of Interest In A Primate
  • Modified Polynucleotides Encoding Aquaporin-5
  • Modified Polynucleotides For The Production Of Proteins Associated With Blood And Lymphatic Disorders
  • Modified Polynucleotides For The Production Of Cytoplasmic And Cytoskeletal Proteins
  • Modified Polynucleotides For The Production Of Cytoplasmic And Cytoskeletal Proteins
  • Split Dose Administration
  • Modified Polynucleotides Encoding Aryl Hydrocarbon Receptor Nuclear Translocator
  • Modified Nucleosides, Nucleotides, And Nucleic Acids, And Uses Thereof
  • Modified Polynucleotides For The Production Of Proteins Associated With Blood And Lymphatic Disorders
  • Modified Polynucleotides For The Production Of Biologics And Proteins Associated With Human Disease
  • Formulation And Delivery Of Plga Microspheres
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/362171a0

    DOI

    http://dx.doi.org/10.1038/362171a0

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1050129386

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/7680770


    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/2008/0604", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Genetics", 
            "type": "DefinedTerm"
          }, 
          {
            "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"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Alternative Splicing", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Animals", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Animals, Genetically Modified", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Base Sequence", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Drosophila Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Drosophila melanogaster", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Female", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Genes, Lethal", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Globins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Insect Hormones", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Introns", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Male", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Molecular Sequence Data", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Nuclear Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Polymerase Chain Reaction", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "RNA", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "RNA Precursors", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "RNA Splicing", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "RNA-Binding Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Recombinant Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Ribonucleoproteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Sex Ratio", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Splicing Factor U2AF", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "UMass Memorial Medical Center", 
              "id": "https://www.grid.ac/institutes/grid.416999.a", 
              "name": [
                "Program in Molecular Medicine, University of Massachusetts Medical Center, Worcester 01605."
              ], 
              "type": "Organization"
            }, 
            "familyName": "Valc\u00e1rcel", 
            "givenName": "J", 
            "id": "sg:person.01152232272.14", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01152232272.14"
            ], 
            "type": "Person"
          }, 
          {
            "familyName": "Singh", 
            "givenName": "R", 
            "id": "sg:person.01324472003.48", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01324472003.48"
            ], 
            "type": "Person"
          }, 
          {
            "familyName": "Zamore", 
            "givenName": "P D", 
            "id": "sg:person.0736647163.00", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0736647163.00"
            ], 
            "type": "Person"
          }, 
          {
            "familyName": "Green", 
            "givenName": "M R", 
            "id": "sg:person.016667213772.00", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016667213772.00"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "https://doi.org/10.1016/0092-8674(89)90426-1", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001394261"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0092-8674(88)90509-0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1006698853"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0092-8674(87)90202-9", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1006725418"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1146/annurev.ge.22.120188.002131", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1009000510"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0092-8674(88)90384-4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1012950367"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/nar/12.18.7035", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1014577216"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0092-8674(91)90321-o", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1015765156"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1101/gad.5.11.2071", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1022259598"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0092-8674(89)90619-3", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024960653"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0022-2836(86)90385-2", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1027376608"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/355609a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1028041675", 
              "https://doi.org/10.1038/355609a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/nar/15.21.8783", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030547335"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0092-8674(84)90049-7", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1031055918"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0092-8674(88)90248-6", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032903375"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/nar/20.21.5533", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1037535746"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0092-8674(91)90090-l", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1038270498"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0092-8674(87)90332-1", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1041864610"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/340521a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1046482747", 
              "https://doi.org/10.1038/340521a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/344461a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1049238541", 
              "https://doi.org/10.1038/344461a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0378-1119(88)90005-4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1049548272"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0378-1119(88)90005-4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1049548272"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/nar/17.7.2655", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1050017894"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.1902987", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1062512945"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.2161558", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1062525117"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.3544217", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1062619940"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1074562114", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/j.1460-2075.1990.tb07441.x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1077292348"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/j.1460-2075.1991.tb07937.x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1077602974"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "1993-03", 
        "datePublishedReg": "1993-03-01", 
        "description": "Somatic sexual differentiation in Drosophila melanogaster involves a cascade of regulated splicing events and provides an attractive model system for the analysis of alternative splicing mechanisms. The protein Sex-lethal (Sxl) activates a female-specific 3' splice site in the first intron of transformer (tra) pre-mRNA while repressing an alternative non-sex-specific site. We have developed an in vitro system that recapitulates this regulation in a manner consistent with genetic, transfection and fly transformation studies. Using this system, we have determined the molecular basis of the splice site switch. Here we show that Sxl inhibits splicing to the non-sex-specific (default) site by specifically binding to its polypyrimidine tract, blocking the binding of the essential splicing factor U2AF. This enables U2AF to activate the lower-affinity female-specific site. A splicing 'effector' domain present in U2AF but absent from Sxl accounts for the different activities of these two polypyrimidine-tract-binding proteins: addition of the U2AF effector domain to Sxl converts it from a splicing repressor to an activator and renders it unable to mediate splice-site switching.", 
        "genre": "research_article", 
        "id": "sg:pub.10.1038/362171a0", 
        "inLanguage": [
          "en"
        ], 
        "isAccessibleForFree": false, 
        "isPartOf": [
          {
            "id": "sg:journal.1018957", 
            "issn": [
              "0090-0028", 
              "1476-4687"
            ], 
            "name": "Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "6416", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "362"
          }
        ], 
        "name": "The protein Sex-lethal antagonizes the splicing factor U2AF to regulate alternative splicing of transformer pre-mRNA", 
        "pagination": "171-175", 
        "productId": [
          {
            "name": "readcube_id", 
            "type": "PropertyValue", 
            "value": [
              "eecd359c11b07ed59f8999db49456ca27566644de9d0011811dc36fefa5d1a1f"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "7680770"
            ]
          }, 
          {
            "name": "nlm_unique_id", 
            "type": "PropertyValue", 
            "value": [
              "0410462"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/362171a0"
            ]
          }, 
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1050129386"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/362171a0", 
          "https://app.dimensions.ai/details/publication/pub.1050129386"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2019-04-11T01:47", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000001_0000000264/records_8700_00000426.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "http://www.nature.com/articles/362171a0"
      }
    ]
     

    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.10.1038/362171a0'

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

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/362171a0'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/362171a0'

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

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/362171a0'


     

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

    266 TRIPLES      21 PREDICATES      80 URIs      45 LITERALS      33 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/362171a0 schema:about N08c666049a55423d9a9b5e48748196ce
    2 N0d8e7f710e9a4b868d3088d58916849a
    3 N1bdc413a31174f6d9d5b45cb4c134076
    4 N2025f8a5d6194f9b89c794c426824889
    5 N2770a6a4c88d4d4ea24db446def0ab7b
    6 N3f4a79dc11ae4cae9f4fec8fff50e214
    7 N42c16a2a2a0940318eff439350c41b0c
    8 N4c1a37fd1940447aa7f255ea8a74bc9b
    9 N5574e20817f043f8bda3e2e2ee6eb96f
    10 N5b8e1c74e4f54237a7257b80e5f2a43a
    11 N5efe5fd974094225a8fe841a13da0125
    12 N74b19826f08548b0acc42eb821ed22e8
    13 N820e9842508e4b998672eeb1cde85469
    14 N8973265b228648de8a5fc3f049552758
    15 N92e83c09b7a34359a29d88da47f90a3f
    16 Na019b5093e444a14b87340748013dfdd
    17 Naa3efd643db04265b3aab2300f118ad6
    18 Nab6cf585fa744110a865c58f9aa7545c
    19 Nb1f133eae328498ba878efb80490ed35
    20 Nb8e475847fbd40a8a53fbe562265cd05
    21 Nd07cd23f3961419d93247c8acedfd0e9
    22 Nd3139cca902f43b0887717360df8778c
    23 Ndc34bb10686345488d96d967ea441a8a
    24 Ne7fe0fa218834f179a11db89569aad54
    25 anzsrc-for:06
    26 anzsrc-for:0604
    27 schema:author N43a49788a83e475b909e6baeffa3e76c
    28 schema:citation sg:pub.10.1038/340521a0
    29 sg:pub.10.1038/344461a0
    30 sg:pub.10.1038/355609a0
    31 https://app.dimensions.ai/details/publication/pub.1074562114
    32 https://doi.org/10.1002/j.1460-2075.1990.tb07441.x
    33 https://doi.org/10.1002/j.1460-2075.1991.tb07937.x
    34 https://doi.org/10.1016/0022-2836(86)90385-2
    35 https://doi.org/10.1016/0092-8674(84)90049-7
    36 https://doi.org/10.1016/0092-8674(87)90202-9
    37 https://doi.org/10.1016/0092-8674(87)90332-1
    38 https://doi.org/10.1016/0092-8674(88)90248-6
    39 https://doi.org/10.1016/0092-8674(88)90384-4
    40 https://doi.org/10.1016/0092-8674(88)90509-0
    41 https://doi.org/10.1016/0092-8674(89)90426-1
    42 https://doi.org/10.1016/0092-8674(89)90619-3
    43 https://doi.org/10.1016/0092-8674(91)90090-l
    44 https://doi.org/10.1016/0092-8674(91)90321-o
    45 https://doi.org/10.1016/0378-1119(88)90005-4
    46 https://doi.org/10.1093/nar/12.18.7035
    47 https://doi.org/10.1093/nar/15.21.8783
    48 https://doi.org/10.1093/nar/17.7.2655
    49 https://doi.org/10.1093/nar/20.21.5533
    50 https://doi.org/10.1101/gad.5.11.2071
    51 https://doi.org/10.1126/science.1902987
    52 https://doi.org/10.1126/science.2161558
    53 https://doi.org/10.1126/science.3544217
    54 https://doi.org/10.1146/annurev.ge.22.120188.002131
    55 schema:datePublished 1993-03
    56 schema:datePublishedReg 1993-03-01
    57 schema:description Somatic sexual differentiation in Drosophila melanogaster involves a cascade of regulated splicing events and provides an attractive model system for the analysis of alternative splicing mechanisms. The protein Sex-lethal (Sxl) activates a female-specific 3' splice site in the first intron of transformer (tra) pre-mRNA while repressing an alternative non-sex-specific site. We have developed an in vitro system that recapitulates this regulation in a manner consistent with genetic, transfection and fly transformation studies. Using this system, we have determined the molecular basis of the splice site switch. Here we show that Sxl inhibits splicing to the non-sex-specific (default) site by specifically binding to its polypyrimidine tract, blocking the binding of the essential splicing factor U2AF. This enables U2AF to activate the lower-affinity female-specific site. A splicing 'effector' domain present in U2AF but absent from Sxl accounts for the different activities of these two polypyrimidine-tract-binding proteins: addition of the U2AF effector domain to Sxl converts it from a splicing repressor to an activator and renders it unable to mediate splice-site switching.
    58 schema:genre research_article
    59 schema:inLanguage en
    60 schema:isAccessibleForFree false
    61 schema:isPartOf N67d7977fecec46c6bc058bc609d5969a
    62 N6dcf8338920e4b8382ce138d1542e735
    63 sg:journal.1018957
    64 schema:name The protein Sex-lethal antagonizes the splicing factor U2AF to regulate alternative splicing of transformer pre-mRNA
    65 schema:pagination 171-175
    66 schema:productId N0ed4be4a43a74c0cbcf293d01d84ee8a
    67 N43e1baedec5e410e9113730c42d43fa2
    68 N99b67d5971af46a0b623ac2a5dd073ea
    69 Na6f739f99c524a88a9e21646f9e8e072
    70 Nbf35fb0328c2411e9c60af7625972c65
    71 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050129386
    72 https://doi.org/10.1038/362171a0
    73 schema:sdDatePublished 2019-04-11T01:47
    74 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    75 schema:sdPublisher N19847f3199e24548abe8162bc01d0f83
    76 schema:url http://www.nature.com/articles/362171a0
    77 sgo:license sg:explorer/license/
    78 sgo:sdDataset articles
    79 rdf:type schema:ScholarlyArticle
    80 N08c666049a55423d9a9b5e48748196ce schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    81 schema:name Polymerase Chain Reaction
    82 rdf:type schema:DefinedTerm
    83 N0d8e7f710e9a4b868d3088d58916849a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    84 schema:name Insect Hormones
    85 rdf:type schema:DefinedTerm
    86 N0ed4be4a43a74c0cbcf293d01d84ee8a schema:name doi
    87 schema:value 10.1038/362171a0
    88 rdf:type schema:PropertyValue
    89 N10323f4dca0440ac80b05d14aadb9bb9 rdf:first sg:person.0736647163.00
    90 rdf:rest Nb1bc000e2e7f470ca192b9e8deb6a564
    91 N19847f3199e24548abe8162bc01d0f83 schema:name Springer Nature - SN SciGraph project
    92 rdf:type schema:Organization
    93 N1bdc413a31174f6d9d5b45cb4c134076 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    94 schema:name Sex Ratio
    95 rdf:type schema:DefinedTerm
    96 N2025f8a5d6194f9b89c794c426824889 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    97 schema:name Molecular Sequence Data
    98 rdf:type schema:DefinedTerm
    99 N2770a6a4c88d4d4ea24db446def0ab7b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    100 schema:name Recombinant Proteins
    101 rdf:type schema:DefinedTerm
    102 N38dd3f03f53c4d388a214c713953e25a rdf:first sg:person.01324472003.48
    103 rdf:rest N10323f4dca0440ac80b05d14aadb9bb9
    104 N3f4a79dc11ae4cae9f4fec8fff50e214 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    105 schema:name Base Sequence
    106 rdf:type schema:DefinedTerm
    107 N42c16a2a2a0940318eff439350c41b0c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    108 schema:name Globins
    109 rdf:type schema:DefinedTerm
    110 N43a49788a83e475b909e6baeffa3e76c rdf:first sg:person.01152232272.14
    111 rdf:rest N38dd3f03f53c4d388a214c713953e25a
    112 N43e1baedec5e410e9113730c42d43fa2 schema:name pubmed_id
    113 schema:value 7680770
    114 rdf:type schema:PropertyValue
    115 N4c1a37fd1940447aa7f255ea8a74bc9b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    116 schema:name Animals
    117 rdf:type schema:DefinedTerm
    118 N5574e20817f043f8bda3e2e2ee6eb96f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    119 schema:name RNA
    120 rdf:type schema:DefinedTerm
    121 N5b8e1c74e4f54237a7257b80e5f2a43a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    122 schema:name Ribonucleoproteins
    123 rdf:type schema:DefinedTerm
    124 N5efe5fd974094225a8fe841a13da0125 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    125 schema:name RNA Precursors
    126 rdf:type schema:DefinedTerm
    127 N67d7977fecec46c6bc058bc609d5969a schema:volumeNumber 362
    128 rdf:type schema:PublicationVolume
    129 N6dcf8338920e4b8382ce138d1542e735 schema:issueNumber 6416
    130 rdf:type schema:PublicationIssue
    131 N74b19826f08548b0acc42eb821ed22e8 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    132 schema:name Alternative Splicing
    133 rdf:type schema:DefinedTerm
    134 N820e9842508e4b998672eeb1cde85469 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    135 schema:name Drosophila Proteins
    136 rdf:type schema:DefinedTerm
    137 N8973265b228648de8a5fc3f049552758 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    138 schema:name Splicing Factor U2AF
    139 rdf:type schema:DefinedTerm
    140 N92e83c09b7a34359a29d88da47f90a3f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    141 schema:name RNA Splicing
    142 rdf:type schema:DefinedTerm
    143 N99b67d5971af46a0b623ac2a5dd073ea schema:name readcube_id
    144 schema:value eecd359c11b07ed59f8999db49456ca27566644de9d0011811dc36fefa5d1a1f
    145 rdf:type schema:PropertyValue
    146 Na019b5093e444a14b87340748013dfdd schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    147 schema:name Male
    148 rdf:type schema:DefinedTerm
    149 Na6f739f99c524a88a9e21646f9e8e072 schema:name dimensions_id
    150 schema:value pub.1050129386
    151 rdf:type schema:PropertyValue
    152 Naa3efd643db04265b3aab2300f118ad6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    153 schema:name Genes, Lethal
    154 rdf:type schema:DefinedTerm
    155 Nab6cf585fa744110a865c58f9aa7545c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    156 schema:name Animals, Genetically Modified
    157 rdf:type schema:DefinedTerm
    158 Nb1bc000e2e7f470ca192b9e8deb6a564 rdf:first sg:person.016667213772.00
    159 rdf:rest rdf:nil
    160 Nb1f133eae328498ba878efb80490ed35 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    161 schema:name Humans
    162 rdf:type schema:DefinedTerm
    163 Nb8e475847fbd40a8a53fbe562265cd05 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    164 schema:name Drosophila melanogaster
    165 rdf:type schema:DefinedTerm
    166 Nbf35fb0328c2411e9c60af7625972c65 schema:name nlm_unique_id
    167 schema:value 0410462
    168 rdf:type schema:PropertyValue
    169 Nd07cd23f3961419d93247c8acedfd0e9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    170 schema:name Nuclear Proteins
    171 rdf:type schema:DefinedTerm
    172 Nd3139cca902f43b0887717360df8778c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    173 schema:name Female
    174 rdf:type schema:DefinedTerm
    175 Ndc34bb10686345488d96d967ea441a8a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    176 schema:name Introns
    177 rdf:type schema:DefinedTerm
    178 Ne7fe0fa218834f179a11db89569aad54 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    179 schema:name RNA-Binding Proteins
    180 rdf:type schema:DefinedTerm
    181 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
    182 schema:name Biological Sciences
    183 rdf:type schema:DefinedTerm
    184 anzsrc-for:0604 schema:inDefinedTermSet anzsrc-for:
    185 schema:name Genetics
    186 rdf:type schema:DefinedTerm
    187 sg:journal.1018957 schema:issn 0090-0028
    188 1476-4687
    189 schema:name Nature
    190 rdf:type schema:Periodical
    191 sg:person.01152232272.14 schema:affiliation https://www.grid.ac/institutes/grid.416999.a
    192 schema:familyName Valcárcel
    193 schema:givenName J
    194 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01152232272.14
    195 rdf:type schema:Person
    196 sg:person.01324472003.48 schema:familyName Singh
    197 schema:givenName R
    198 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01324472003.48
    199 rdf:type schema:Person
    200 sg:person.016667213772.00 schema:familyName Green
    201 schema:givenName M R
    202 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016667213772.00
    203 rdf:type schema:Person
    204 sg:person.0736647163.00 schema:familyName Zamore
    205 schema:givenName P D
    206 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0736647163.00
    207 rdf:type schema:Person
    208 sg:pub.10.1038/340521a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046482747
    209 https://doi.org/10.1038/340521a0
    210 rdf:type schema:CreativeWork
    211 sg:pub.10.1038/344461a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049238541
    212 https://doi.org/10.1038/344461a0
    213 rdf:type schema:CreativeWork
    214 sg:pub.10.1038/355609a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028041675
    215 https://doi.org/10.1038/355609a0
    216 rdf:type schema:CreativeWork
    217 https://app.dimensions.ai/details/publication/pub.1074562114 schema:CreativeWork
    218 https://doi.org/10.1002/j.1460-2075.1990.tb07441.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1077292348
    219 rdf:type schema:CreativeWork
    220 https://doi.org/10.1002/j.1460-2075.1991.tb07937.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1077602974
    221 rdf:type schema:CreativeWork
    222 https://doi.org/10.1016/0022-2836(86)90385-2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027376608
    223 rdf:type schema:CreativeWork
    224 https://doi.org/10.1016/0092-8674(84)90049-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031055918
    225 rdf:type schema:CreativeWork
    226 https://doi.org/10.1016/0092-8674(87)90202-9 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006725418
    227 rdf:type schema:CreativeWork
    228 https://doi.org/10.1016/0092-8674(87)90332-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041864610
    229 rdf:type schema:CreativeWork
    230 https://doi.org/10.1016/0092-8674(88)90248-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032903375
    231 rdf:type schema:CreativeWork
    232 https://doi.org/10.1016/0092-8674(88)90384-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012950367
    233 rdf:type schema:CreativeWork
    234 https://doi.org/10.1016/0092-8674(88)90509-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006698853
    235 rdf:type schema:CreativeWork
    236 https://doi.org/10.1016/0092-8674(89)90426-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001394261
    237 rdf:type schema:CreativeWork
    238 https://doi.org/10.1016/0092-8674(89)90619-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024960653
    239 rdf:type schema:CreativeWork
    240 https://doi.org/10.1016/0092-8674(91)90090-l schema:sameAs https://app.dimensions.ai/details/publication/pub.1038270498
    241 rdf:type schema:CreativeWork
    242 https://doi.org/10.1016/0092-8674(91)90321-o schema:sameAs https://app.dimensions.ai/details/publication/pub.1015765156
    243 rdf:type schema:CreativeWork
    244 https://doi.org/10.1016/0378-1119(88)90005-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049548272
    245 rdf:type schema:CreativeWork
    246 https://doi.org/10.1093/nar/12.18.7035 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014577216
    247 rdf:type schema:CreativeWork
    248 https://doi.org/10.1093/nar/15.21.8783 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030547335
    249 rdf:type schema:CreativeWork
    250 https://doi.org/10.1093/nar/17.7.2655 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050017894
    251 rdf:type schema:CreativeWork
    252 https://doi.org/10.1093/nar/20.21.5533 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037535746
    253 rdf:type schema:CreativeWork
    254 https://doi.org/10.1101/gad.5.11.2071 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022259598
    255 rdf:type schema:CreativeWork
    256 https://doi.org/10.1126/science.1902987 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062512945
    257 rdf:type schema:CreativeWork
    258 https://doi.org/10.1126/science.2161558 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062525117
    259 rdf:type schema:CreativeWork
    260 https://doi.org/10.1126/science.3544217 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062619940
    261 rdf:type schema:CreativeWork
    262 https://doi.org/10.1146/annurev.ge.22.120188.002131 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009000510
    263 rdf:type schema:CreativeWork
    264 https://www.grid.ac/institutes/grid.416999.a schema:alternateName UMass Memorial Medical Center
    265 schema:name Program in Molecular Medicine, University of Massachusetts Medical Center, Worcester 01605.
    266 rdf:type schema:Organization
     




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


    ...