{"doi":"10.1016/j.cell.2015.09.015","title":"Phase Separation by Low Complexity Domains Promotes Stress Granule Assembly and Drives Pathological Fibrillization","abstract":null,"journal":"Cell","year":2015,"id":593133,"datarank":13.938619076222679,"base_score":7.956476798036782,"endowment":7.956476798036782,"self_citation_contribution":1.1934715197055175,"citation_network_contribution":12.745147556517162,"self_endowment_contribution":1.1934715197055175,"citer_contribution":12.745147556517162,"corpus_percentile":null,"corpus_rank":null,"citation_count":2853,"citer_count":200,"citers_with_citation_signal":200,"citers_with_endowment":200,"datacite_reuse_total":25,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":453711,"name":"Jamshid Temirov","orcid":null,"position":1,"is_corresponding":false},{"id":1081151,"name":"Jihun Lee","orcid":"0000-0002-8803-7689","position":2,"is_corresponding":false},{"id":309650,"name":"Maura Coughlin","orcid":null,"position":3,"is_corresponding":false},{"id":1518028,"name":"Anderson P. Kanagaraj","orcid":null,"position":4,"is_corresponding":false},{"id":1518029,"name":"Hong Joo Kim","orcid":null,"position":5,"is_corresponding":false},{"id":257878,"name":"Tanja Mittag","orcid":"0000-0002-1827-3811","position":6,"is_corresponding":false},{"id":1518030,"name":"J. Paul Taylor","orcid":null,"position":7,"is_corresponding":false},{"id":1168701,"name":"Amandine Molliex","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Phase Separation by Low Complexity Domains Promotes Stress Granule Assembly and Drives Pathological Fibrillization","abstract":"Stress granules are membrane-less organelles composed of RNA-binding proteins (RBPs) and RNA. Functional impairment of stress granules has been implicated in amyotrophic lateral sclerosis, frontotemporal dementia, and multisystem proteinopathy-diseases that are characterized by fibrillar inclusions of RBPs. Genetic evidence suggests a link between persistent stress granules and the accumulation of pathological inclusions. Here, we demonstrate that the disease-related RBP hnRNPA1 undergoes liquid-liquid phase separation (LLPS) into protein-rich droplets mediated by a low complexity sequence domain (LCD). While the LCD of hnRNPA1 is sufficient to mediate LLPS, the RNA recognition motifs contribute to LLPS in the presence of RNA, giving rise to several mechanisms for regulating assembly. Importantly, while not required for LLPS, fibrillization is enhanced in protein-rich droplets. We suggest that LCD-mediated LLPS contributes to the assembly of stress granules and their liquid properties and provides a mechanistic link between persistent stress granules and fibrillar protein pathology in disease.","is_dataset_classified":null,"base_score":7.956476798036782,"endowment":7.956476798036782,"datacite_reuse_total":25,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26406374","pmcid":"PMC5149108","openalex_id":"https://openalex.org/W2150860983","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"P30 CA021765","title":null},{"funder_name":"Howard Hughes Medical 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Research and Splicing","biodegradable polymer synthesis and properties","Orthopaedic implants and arthroplasty"],"mesh_terms":["Heterogeneous Nuclear Ribonucleoprotein A1","Amyloid","Cytoplasmic Granules","DNA-Binding Proteins","HeLa Cells","Humans","Heterogeneous-Nuclear Ribonucleoprotein Group A-B","Cell Line, Tumor","Protein Aggregation, Pathological","Hela Cells"],"keywords":["Biology","Stress granule","Granule (geology)","Pathological","Cell biology","Biophysics","Biochemistry","Gene","Internal medicine"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life in Land"}],"linked_datasets":[{"doi":"10.6084/m9.figshare.14738715.v1","title":"Additional file 2 of Sequence determinants of in cell condensate morphology, dynamics, and oligomerization as measured by number and brightness analysis","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14738715","title":"Additional file 2 of Sequence determinants of in cell condensate morphology, dynamics, and 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