Ontology type: schema:ScholarlyArticle Open Access: True
2013-03-03
AUTHORSHong Joo Kim, Nam Chul Kim, Yong-Dong Wang, Emily A. Scarborough, Jennifer Moore, Zamia Diaz, Kyle S. MacLea, Brian Freibaum, Songqing Li, Amandine Molliex, Anderson P. Kanagaraj, Robert Carter, Kevin B. Boylan, Aleksandra M. Wojtas, Rosa Rademakers, Jack L. Pinkus, Steven A. Greenberg, John Q. Trojanowski, Bryan J. Traynor, Bradley N. Smith, Simon Topp, Athina-Soragia Gkazi, Jack Miller, Christopher E. Shaw, Michael Kottlors, Janbernd Kirschner, Alan Pestronk, Yun R. Li, Alice Flynn Ford, Aaron D. Gitler, Michael Benatar, Oliver D. King, Virginia E. Kimonis, Eric D. Ross, Conrad C. Weihl, James Shorter, J. Paul Taylor
ABSTRACTAlgorithms designed to identify canonical yeast prions predict that around 250 human proteins, including several RNA-binding proteins associated with neurodegenerative disease, harbour a distinctive prion-like domain (PrLD) enriched in uncharged polar amino acids and glycine. PrLDs in RNA-binding proteins are essential for the assembly of ribonucleoprotein granules. However, the interplay between human PrLD function and disease is not understood. Here we define pathogenic mutations in PrLDs of heterogeneous nuclear ribonucleoproteins (hnRNPs) A2B1 and A1 in families with inherited degeneration affecting muscle, brain, motor neuron and bone, and in one case of familial amyotrophic lateral sclerosis. Wild-type hnRNPA2 (the most abundant isoform of hnRNPA2B1) and hnRNPA1 show an intrinsic tendency to assemble into self-seeding fibrils, which is exacerbated by the disease mutations. Indeed, the pathogenic mutations strengthen a ‘steric zipper’ motif in the PrLD, which accelerates the formation of self-seeding fibrils that cross-seed polymerization of wild-type hnRNP. Notably, the disease mutations promote excess incorporation of hnRNPA2 and hnRNPA1 into stress granules and drive the formation of cytoplasmic inclusions in animal models that recapitulate the human pathology. Thus, dysregulated polymerization caused by a potent mutant steric zipper motif in a PrLD can initiate degenerative disease. Related proteins with PrLDs should therefore be considered candidates for initiating and perhaps propagating proteinopathies of muscle, brain, motor neuron and bone. More... »
PAGES467-473
http://scigraph.springernature.com/pub.10.1038/nature11922
DOIhttp://dx.doi.org/10.1038/nature11922
DIMENSIONShttps://app.dimensions.ai/details/publication/pub.1037021180
PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/23455423
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/2008/11",
"inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/",
"name": "Medical and Health Sciences",
"type": "DefinedTerm"
},
{
"id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0601",
"inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/",
"name": "Biochemistry and Cell Biology",
"type": "DefinedTerm"
},
{
"id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1109",
"inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/",
"name": "Neurosciences",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Amino Acid Sequence",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Amyotrophic Lateral Sclerosis",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Animals",
"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": "Frontotemporal Dementia",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "HeLa Cells",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Heterogeneous-Nuclear Ribonucleoprotein Group A-B",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Humans",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Inclusion Bodies",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Male",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Mice",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Molecular Sequence Data",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Muscular Dystrophies, Limb-Girdle",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Mutant Proteins",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Mutation",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Myositis, Inclusion Body",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Osteitis Deformans",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Peptide Termination Factors",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Prions",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Protein Structure, Tertiary",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "RNA",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Saccharomyces cerevisiae Proteins",
"type": "DefinedTerm"
}
],
"author": [
{
"affiliation": {
"alternateName": "Department of Developmental Neurobiology, St Jude Children\u2019s Research Hospital, 38120, Memphis, Tennessee, USA",
"id": "http://www.grid.ac/institutes/grid.240871.8",
"name": [
"Department of Developmental Neurobiology, St Jude Children\u2019s Research Hospital, 38120, Memphis, Tennessee, USA"
],
"type": "Organization"
},
"familyName": "Kim",
"givenName": "Hong Joo",
"id": "sg:person.01176644355.00",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01176644355.00"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Developmental Neurobiology, St Jude Children\u2019s Research Hospital, 38120, Memphis, Tennessee, USA",
"id": "http://www.grid.ac/institutes/grid.240871.8",
"name": [
"Department of Developmental Neurobiology, St Jude Children\u2019s Research Hospital, 38120, Memphis, Tennessee, USA"
],
"type": "Organization"
},
"familyName": "Kim",
"givenName": "Nam Chul",
"id": "sg:person.01127334262.78",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01127334262.78"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Hartwell Center for Bioinformatics and Biotechnology, St Jude Children\u2019s Research Hospital, 38120, Memphis, Tennessee, USA",
"id": "http://www.grid.ac/institutes/grid.240871.8",
"name": [
"Hartwell Center for Bioinformatics and Biotechnology, St Jude Children\u2019s Research Hospital, 38120, Memphis, Tennessee, USA"
],
"type": "Organization"
},
"familyName": "Wang",
"givenName": "Yong-Dong",
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, 19104, Philadelphia, Pennsylvania, USA",
"id": "http://www.grid.ac/institutes/grid.25879.31",
"name": [
"Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, 19104, Philadelphia, Pennsylvania, USA"
],
"type": "Organization"
},
"familyName": "Scarborough",
"givenName": "Emily A.",
"id": "sg:person.01052535702.65",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01052535702.65"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Developmental Neurobiology, St Jude Children\u2019s Research Hospital, 38120, Memphis, Tennessee, USA",
"id": "http://www.grid.ac/institutes/grid.240871.8",
"name": [
"Department of Developmental Neurobiology, St Jude Children\u2019s Research Hospital, 38120, Memphis, Tennessee, USA"
],
"type": "Organization"
},
"familyName": "Moore",
"givenName": "Jennifer",
"id": "sg:person.01201310562.25",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01201310562.25"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, 19104, Philadelphia, Pennsylvania, USA",
"id": "http://www.grid.ac/institutes/grid.25879.31",
"name": [
"Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, 19104, Philadelphia, Pennsylvania, USA"
],
"type": "Organization"
},
"familyName": "Diaz",
"givenName": "Zamia",
"id": "sg:person.01165040350.56",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01165040350.56"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Biochemistry and Molecular Biology, Colorado State University, 80523, Fort Collins, Colorado, USA",
"id": "http://www.grid.ac/institutes/grid.47894.36",
"name": [
"Department of Biochemistry and Molecular Biology, Colorado State University, 80523, Fort Collins, Colorado, USA"
],
"type": "Organization"
},
"familyName": "MacLea",
"givenName": "Kyle S.",
"id": "sg:person.01055662734.77",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01055662734.77"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Developmental Neurobiology, St Jude Children\u2019s Research Hospital, 38120, Memphis, Tennessee, USA",
"id": "http://www.grid.ac/institutes/grid.240871.8",
"name": [
"Department of Developmental Neurobiology, St Jude Children\u2019s Research Hospital, 38120, Memphis, Tennessee, USA"
],
"type": "Organization"
},
"familyName": "Freibaum",
"givenName": "Brian",
"id": "sg:person.01036663113.01",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01036663113.01"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Developmental Neurobiology, St Jude Children\u2019s Research Hospital, 38120, Memphis, Tennessee, USA",
"id": "http://www.grid.ac/institutes/grid.240871.8",
"name": [
"Department of Developmental Neurobiology, St Jude Children\u2019s Research Hospital, 38120, Memphis, Tennessee, USA"
],
"type": "Organization"
},
"familyName": "Li",
"givenName": "Songqing",
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Developmental Neurobiology, St Jude Children\u2019s Research Hospital, 38120, Memphis, Tennessee, USA",
"id": "http://www.grid.ac/institutes/grid.240871.8",
"name": [
"Department of Developmental Neurobiology, St Jude Children\u2019s Research Hospital, 38120, Memphis, Tennessee, USA"
],
"type": "Organization"
},
"familyName": "Molliex",
"givenName": "Amandine",
"id": "sg:person.01002107304.04",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01002107304.04"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Developmental Neurobiology, St Jude Children\u2019s Research Hospital, 38120, Memphis, Tennessee, USA",
"id": "http://www.grid.ac/institutes/grid.240871.8",
"name": [
"Department of Developmental Neurobiology, St Jude Children\u2019s Research Hospital, 38120, Memphis, Tennessee, USA"
],
"type": "Organization"
},
"familyName": "Kanagaraj",
"givenName": "Anderson P.",
"id": "sg:person.0653164337.44",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0653164337.44"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Computational Biology, St Jude Children\u2019s Research Hospital, 38120, Memphis, Tennessee, USA",
"id": "http://www.grid.ac/institutes/grid.240871.8",
"name": [
"Department of Computational Biology, St Jude Children\u2019s Research Hospital, 38120, Memphis, Tennessee, USA"
],
"type": "Organization"
},
"familyName": "Carter",
"givenName": "Robert",
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Neuroscience, Mayo Clinic, 32224, Jacksonville, Florida, USA",
"id": "http://www.grid.ac/institutes/grid.417467.7",
"name": [
"Department of Neuroscience, Mayo Clinic, 32224, Jacksonville, Florida, USA"
],
"type": "Organization"
},
"familyName": "Boylan",
"givenName": "Kevin B.",
"id": "sg:person.01016121034.80",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01016121034.80"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Neuroscience, Mayo Clinic, 32224, Jacksonville, Florida, USA",
"id": "http://www.grid.ac/institutes/grid.417467.7",
"name": [
"Department of Neuroscience, Mayo Clinic, 32224, Jacksonville, Florida, USA"
],
"type": "Organization"
},
"familyName": "Wojtas",
"givenName": "Aleksandra M.",
"id": "sg:person.01015313604.68",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01015313604.68"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Neuroscience, Mayo Clinic, 32224, Jacksonville, Florida, USA",
"id": "http://www.grid.ac/institutes/grid.417467.7",
"name": [
"Department of Neuroscience, Mayo Clinic, 32224, Jacksonville, Florida, USA"
],
"type": "Organization"
},
"familyName": "Rademakers",
"givenName": "Rosa",
"id": "sg:person.01370327406.42",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01370327406.42"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Neurology, Brigham and Women\u2019s Hospital, Harvard Medical School, 02115, Boston, Massachusetts, USA",
"id": "http://www.grid.ac/institutes/grid.62560.37",
"name": [
"Department of Neurology, Brigham and Women\u2019s Hospital, Harvard Medical School, 02115, Boston, Massachusetts, USA"
],
"type": "Organization"
},
"familyName": "Pinkus",
"givenName": "Jack L.",
"id": "sg:person.0644704467.27",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0644704467.27"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Neurology, Brigham and Women\u2019s Hospital, Harvard Medical School, 02115, Boston, Massachusetts, USA",
"id": "http://www.grid.ac/institutes/grid.62560.37",
"name": [
"Department of Neurology, Brigham and Women\u2019s Hospital, Harvard Medical School, 02115, Boston, Massachusetts, USA"
],
"type": "Organization"
},
"familyName": "Greenberg",
"givenName": "Steven A.",
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, Perelman School of Medicine at the University of Pennsylvania, 19104, Philadelphia, Pennsylvania, USA",
"id": "http://www.grid.ac/institutes/grid.25879.31",
"name": [
"Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, Perelman School of Medicine at the University of Pennsylvania, 19104, Philadelphia, Pennsylvania, USA"
],
"type": "Organization"
},
"familyName": "Trojanowski",
"givenName": "John Q.",
"id": "sg:person.01043025611.21",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01043025611.21"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Neuromuscular Diseases Research Group, Laboratory of Neurogenetics, Porter Neuroscience Building, National Institute on Aging, National Institutes of Health, 20892, Bethesda, Maryland, USA",
"id": "http://www.grid.ac/institutes/grid.94365.3d",
"name": [
"Neuromuscular Diseases Research Group, Laboratory of Neurogenetics, Porter Neuroscience Building, National Institute on Aging, National Institutes of Health, 20892, Bethesda, Maryland, USA"
],
"type": "Organization"
},
"familyName": "Traynor",
"givenName": "Bryan J.",
"id": "sg:person.0651415272.99",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0651415272.99"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, Perelman School of Medicine at the University of Pennsylvania, 19104, Philadelphia, Pennsylvania, USA",
"id": "http://www.grid.ac/institutes/grid.25879.31",
"name": [
"Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, Perelman School of Medicine at the University of Pennsylvania, 19104, Philadelphia, Pennsylvania, USA"
],
"type": "Organization"
},
"familyName": "Smith",
"givenName": "Bradley N.",
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Clinical Neuroscience, King\u2019s College London Centre for Neurodegeneration Research, Institute of Psychiatry, London SE5 8AF, UK",
"id": "http://www.grid.ac/institutes/grid.13097.3c",
"name": [
"Department of Clinical Neuroscience, King\u2019s College London Centre for Neurodegeneration Research, Institute of Psychiatry, London SE5 8AF, UK"
],
"type": "Organization"
},
"familyName": "Topp",
"givenName": "Simon",
"id": "sg:person.01224543341.26",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01224543341.26"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Clinical Neuroscience, King\u2019s College London Centre for Neurodegeneration Research, Institute of Psychiatry, London SE5 8AF, UK",
"id": "http://www.grid.ac/institutes/grid.13097.3c",
"name": [
"Department of Clinical Neuroscience, King\u2019s College London Centre for Neurodegeneration Research, Institute of Psychiatry, London SE5 8AF, UK"
],
"type": "Organization"
},
"familyName": "Gkazi",
"givenName": "Athina-Soragia",
"id": "sg:person.01123524205.63",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01123524205.63"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Clinical Neuroscience, King\u2019s College London Centre for Neurodegeneration Research, Institute of Psychiatry, London SE5 8AF, UK",
"id": "http://www.grid.ac/institutes/grid.13097.3c",
"name": [
"Department of Clinical Neuroscience, King\u2019s College London Centre for Neurodegeneration Research, Institute of Psychiatry, London SE5 8AF, UK"
],
"type": "Organization"
},
"familyName": "Miller",
"givenName": "Jack",
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Clinical Neuroscience, King\u2019s College London Centre for Neurodegeneration Research, Institute of Psychiatry, London SE5 8AF, UK",
"id": "http://www.grid.ac/institutes/grid.13097.3c",
"name": [
"Department of Clinical Neuroscience, King\u2019s College London Centre for Neurodegeneration Research, Institute of Psychiatry, London SE5 8AF, UK"
],
"type": "Organization"
},
"familyName": "Shaw",
"givenName": "Christopher E.",
"id": "sg:person.015122554672.30",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015122554672.30"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Division of Neuropediatrics and Muscle Disorders, University Children\u2019s Hospital Freiburg, 79106 Freiburg, Germany",
"id": "http://www.grid.ac/institutes/grid.7708.8",
"name": [
"Division of Neuropediatrics and Muscle Disorders, University Children\u2019s Hospital Freiburg, 79106 Freiburg, Germany"
],
"type": "Organization"
},
"familyName": "Kottlors",
"givenName": "Michael",
"id": "sg:person.01234254520.02",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01234254520.02"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Division of Neuropediatrics and Muscle Disorders, University Children\u2019s Hospital Freiburg, 79106 Freiburg, Germany",
"id": "http://www.grid.ac/institutes/grid.7708.8",
"name": [
"Division of Neuropediatrics and Muscle Disorders, University Children\u2019s Hospital Freiburg, 79106 Freiburg, Germany"
],
"type": "Organization"
},
"familyName": "Kirschner",
"givenName": "Janbernd",
"id": "sg:person.0717435623.02",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0717435623.02"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Neurology, Washington University School of Medicine, 63110, Saint Louis, Missouri, USA",
"id": "http://www.grid.ac/institutes/grid.4367.6",
"name": [
"Department of Neurology, Washington University School of Medicine, 63110, Saint Louis, Missouri, USA"
],
"type": "Organization"
},
"familyName": "Pestronk",
"givenName": "Alan",
"type": "Person"
},
{
"affiliation": {
"alternateName": "Medical Scientist Training Program, Perelman School of Medicine at the University of Pennsylvania, 19104, Philadelphia, Pennsylvania, USA",
"id": "http://www.grid.ac/institutes/grid.25879.31",
"name": [
"Medical Scientist Training Program, Perelman School of Medicine at the University of Pennsylvania, 19104, Philadelphia, Pennsylvania, USA"
],
"type": "Organization"
},
"familyName": "Li",
"givenName": "Yun R.",
"id": "sg:person.01004153144.54",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01004153144.54"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, 19104, Philadelphia, Pennsylvania, USA",
"id": "http://www.grid.ac/institutes/grid.25879.31",
"name": [
"Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, 19104, Philadelphia, Pennsylvania, USA"
],
"type": "Organization"
},
"familyName": "Ford",
"givenName": "Alice Flynn",
"id": "sg:person.0637134562.09",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0637134562.09"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Genetics, Stanford University School of Medicine, 94305, Stanford, California, USA",
"id": "http://www.grid.ac/institutes/grid.168010.e",
"name": [
"Department of Genetics, Stanford University School of Medicine, 94305, Stanford, California, USA"
],
"type": "Organization"
},
"familyName": "Gitler",
"givenName": "Aaron D.",
"id": "sg:person.01046446465.11",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01046446465.11"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Neurology Department, University of Miami Miller School of Medicine, 33136, Miami, Florida, USA",
"id": "http://www.grid.ac/institutes/grid.26790.3a",
"name": [
"Neurology Department, University of Miami Miller School of Medicine, 33136, Miami, Florida, USA"
],
"type": "Organization"
},
"familyName": "Benatar",
"givenName": "Michael",
"type": "Person"
},
{
"affiliation": {
"alternateName": "Boston Biomedical Research Institute, 02472, Watertown, Massachusetts, USA",
"id": "http://www.grid.ac/institutes/grid.280432.f",
"name": [
"Boston Biomedical Research Institute, 02472, Watertown, Massachusetts, USA"
],
"type": "Organization"
},
"familyName": "King",
"givenName": "Oliver D.",
"id": "sg:person.01241430423.21",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01241430423.21"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Pediatrics, Division of Genetics and Metabolism, University of California-Irvine, 2501 Hewitt Hall, Irvine, California 92696, USA",
"id": "http://www.grid.ac/institutes/grid.266093.8",
"name": [
"Department of Pediatrics, Division of Genetics and Metabolism, University of California-Irvine, 2501 Hewitt Hall, Irvine, California 92696, USA"
],
"type": "Organization"
},
"familyName": "Kimonis",
"givenName": "Virginia E.",
"id": "sg:person.01011236005.03",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01011236005.03"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Biochemistry and Molecular Biology, Colorado State University, 80523, Fort Collins, Colorado, USA",
"id": "http://www.grid.ac/institutes/grid.47894.36",
"name": [
"Department of Biochemistry and Molecular Biology, Colorado State University, 80523, Fort Collins, Colorado, USA"
],
"type": "Organization"
},
"familyName": "Ross",
"givenName": "Eric D.",
"id": "sg:person.01241145525.69",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01241145525.69"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Neurology, Washington University School of Medicine, 63110, Saint Louis, Missouri, USA",
"id": "http://www.grid.ac/institutes/grid.4367.6",
"name": [
"Department of Neurology, Washington University School of Medicine, 63110, Saint Louis, Missouri, USA"
],
"type": "Organization"
},
"familyName": "Weihl",
"givenName": "Conrad C.",
"id": "sg:person.0577617115.87",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0577617115.87"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, 19104, Philadelphia, Pennsylvania, USA",
"id": "http://www.grid.ac/institutes/grid.25879.31",
"name": [
"Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, 19104, Philadelphia, Pennsylvania, USA"
],
"type": "Organization"
},
"familyName": "Shorter",
"givenName": "James",
"id": "sg:person.01235077502.51",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01235077502.51"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Developmental Neurobiology, St Jude Children\u2019s Research Hospital, 38120, Memphis, Tennessee, USA",
"id": "http://www.grid.ac/institutes/grid.240871.8",
"name": [
"Department of Developmental Neurobiology, St Jude Children\u2019s Research Hospital, 38120, Memphis, Tennessee, USA"
],
"type": "Organization"
},
"familyName": "Taylor",
"givenName": "J. Paul",
"id": "sg:person.013436160257.94",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013436160257.94"
],
"type": "Person"
}
],
"citation": [
{
"id": "sg:pub.10.1186/1750-1326-7-56",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1038751873",
"https://doi.org/10.1186/1750-1326-7-56"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1007/978-1-59745-251-9_3",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1018752572",
"https://doi.org/10.1007/978-1-59745-251-9_3"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1007/s12031-011-9627-y",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1043240937",
"https://doi.org/10.1007/s12031-011-9627-y"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/ng1332",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1041421858",
"https://doi.org/10.1038/ng1332"
],
"type": "CreativeWork"
}
],
"datePublished": "2013-03-03",
"datePublishedReg": "2013-03-03",
"description": "Algorithms designed to identify canonical yeast prions predict that around 250 human proteins, including several RNA-binding proteins associated with neurodegenerative disease, harbour a distinctive prion-like domain (PrLD) enriched in uncharged polar amino acids and glycine. PrLDs in RNA-binding proteins are essential for the assembly of ribonucleoprotein granules. However, the interplay between human PrLD function and disease is not understood. Here we define pathogenic mutations in PrLDs of heterogeneous nuclear ribonucleoproteins (hnRNPs) A2B1 and A1 in families with inherited degeneration affecting muscle, brain, motor neuron and bone, and in one case of familial amyotrophic lateral sclerosis. Wild-type hnRNPA2 (the most abundant isoform of hnRNPA2B1) and hnRNPA1 show an intrinsic tendency to assemble into self-seeding fibrils, which is exacerbated by the disease mutations. Indeed, the pathogenic mutations strengthen a \u2018steric zipper\u2019 motif in the PrLD, which accelerates the formation of self-seeding fibrils that cross-seed polymerization of wild-type hnRNP. Notably, the disease mutations promote excess incorporation of hnRNPA2 and hnRNPA1 into stress granules and drive the formation of cytoplasmic inclusions in animal models that recapitulate the human pathology. Thus, dysregulated polymerization caused by a potent mutant steric zipper motif in a PrLD can initiate degenerative disease. Related proteins with PrLDs should therefore be considered candidates for initiating and perhaps propagating proteinopathies of muscle, brain, motor neuron and bone.",
"genre": "article",
"id": "sg:pub.10.1038/nature11922",
"inLanguage": "en",
"isAccessibleForFree": true,
"isFundedItemOf": [
{
"id": "sg:grant.2561589",
"type": "MonetaryGrant"
},
{
"id": "sg:grant.2405872",
"type": "MonetaryGrant"
},
{
"id": "sg:grant.2759579",
"type": "MonetaryGrant"
},
{
"id": "sg:grant.2617738",
"type": "MonetaryGrant"
},
{
"id": "sg:grant.2355250",
"type": "MonetaryGrant"
},
{
"id": "sg:grant.3116644",
"type": "MonetaryGrant"
},
{
"id": "sg:grant.2722925",
"type": "MonetaryGrant"
},
{
"id": "sg:grant.2448404",
"type": "MonetaryGrant"
},
{
"id": "sg:grant.2434811",
"type": "MonetaryGrant"
},
{
"id": "sg:grant.2780245",
"type": "MonetaryGrant"
},
{
"id": "sg:grant.3637675",
"type": "MonetaryGrant"
}
],
"isPartOf": [
{
"id": "sg:journal.1018957",
"issn": [
"0028-0836",
"1476-4687"
],
"name": "Nature",
"publisher": "Springer Nature",
"type": "Periodical"
},
{
"issueNumber": "7442",
"type": "PublicationIssue"
},
{
"type": "PublicationVolume",
"volumeNumber": "495"
}
],
"keywords": [
"heterogeneous nuclear ribonucleoproteins",
"prion-like domains",
"disease mutations",
"uncharged polar amino acids",
"RNA-binding protein",
"polar amino acids",
"pathogenic mutations",
"yeast prions",
"ribonucleoprotein granules",
"stress granules",
"zipper motif",
"steric zipper motif",
"human proteins",
"nuclear ribonucleoprotein",
"related proteins",
"PrLDs",
"familial amyotrophic lateral sclerosis",
"human pathologies",
"amino acids",
"motor neurons",
"multisystem proteinopathy",
"protein",
"inherited degeneration",
"hnRNPA2",
"excess incorporation",
"mutations",
"steric zipper",
"hnRNPA1",
"neurodegenerative diseases",
"motif",
"intrinsic tendency",
"amyotrophic lateral sclerosis",
"proteinopathies",
"degenerative diseases",
"cytoplasmic inclusions",
"ribonucleoprotein",
"lateral sclerosis",
"hnRNPA2B1",
"RNA",
"zipper",
"domain",
"granules",
"prions",
"fibrils",
"animal models",
"assembly",
"neurons",
"disease",
"family",
"glycine",
"formation",
"muscle",
"brain",
"acid",
"bone",
"interplay",
"A1",
"ALS",
"function",
"sclerosis",
"degeneration",
"pathology",
"incorporation",
"candidates",
"cases",
"polymerization",
"inclusion",
"tendency",
"model",
"algorithm"
],
"name": "Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS",
"pagination": "467-473",
"productId": [
{
"name": "dimensions_id",
"type": "PropertyValue",
"value": [
"pub.1037021180"
]
},
{
"name": "doi",
"type": "PropertyValue",
"value": [
"10.1038/nature11922"
]
},
{
"name": "pubmed_id",
"type": "PropertyValue",
"value": [
"23455423"
]
}
],
"sameAs": [
"https://doi.org/10.1038/nature11922",
"https://app.dimensions.ai/details/publication/pub.1037021180"
],
"sdDataset": "articles",
"sdDatePublished": "2022-05-10T10:06",
"sdLicense": "https://scigraph.springernature.com/explorer/license/",
"sdPublisher": {
"name": "Springer Nature - SN SciGraph project",
"type": "Organization"
},
"sdSource": "s3://com-springernature-scigraph/baseset/20220509/entities/gbq_results/article/article_596.jsonl",
"type": "ScholarlyArticle",
"url": "https://doi.org/10.1038/nature11922"
}
]Download the RDF metadata as: json-ld nt turtle xml License info
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/nature11922'
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/nature11922'
Turtle is a human-readable linked data format.
curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/nature11922'
RDF/XML is a standard XML format for linked data.
curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/nature11922'
This table displays all metadata directly associated to this object as RDF triples.
558 TRIPLES
22 PREDICATES
125 URIs
111 LITERALS
30 BLANK NODES