{"id":"https://openalex.org/W4223607069","doi":"https://doi.org/10.1101/2022.04.11.487960","title":"Systematic generation and imaging of tandem repeats reveal multivalent base-pairing as a major determinant of RNA aggregation","display_name":"Systematic generation and imaging of tandem repeats reveal multivalent base-pairing as a major determinant of RNA aggregation","publication_year":2022,"publication_date":"2022-04-12","ids":{"openalex":"https://openalex.org/W4223607069","doi":"https://doi.org/10.1101/2022.04.11.487960"},"language":"en","primary_location":{"id":"doi:10.1101/2022.04.11.487960","doi":"https://doi.org/10.1101/2022.04.11.487960","is_oa":true,"landing_page_url":"https://doi.org/10.1101/2022.04.11.487960","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2022/04/12/2022.04.11.487960.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.biorxiv.org/content/biorxiv/early/2022/04/12/2022.04.11.487960.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5085270759","display_name":"Atagun U. Isiktas","orcid":"https://orcid.org/0000-0002-5459-6810","observed_orcids":["https://orcid.org/0000-0002-5459-6810"]},"institutions":[{"id":"https://openalex.org/I32971472","display_name":"Yale University","ror":"https://ror.org/03v76x132","country_code":"US","type":"education","lineage":["https://openalex.org/I32971472"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Atagun U. Isiktas","raw_affiliation_strings":["Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06520, USA","Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06520, USA","Interdepartmental Neuroscience Program, Yale University, New Haven, CT 0650, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06520, USA","institution_ids":["https://openalex.org/I32971472"]},{"raw_affiliation_string":"Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06520, USA","institution_ids":["https://openalex.org/I32971472"]},{"raw_affiliation_string":"Interdepartmental Neuroscience Program, Yale University, New Haven, CT 0650, USA","institution_ids":["https://openalex.org/I32971472"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5003062362","display_name":"Aziz Eshov","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I32971472","display_name":"Yale University","ror":"https://ror.org/03v76x132","country_code":"US","type":"education","lineage":["https://openalex.org/I32971472"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Aziz Eshov","raw_affiliation_strings":["Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06520, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06520, USA","institution_ids":["https://openalex.org/I32971472"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5051020551","display_name":"Suzhou Yang","orcid":"https://orcid.org/0000-0002-2640-5511","observed_orcids":["https://orcid.org/0000-0002-2640-5511"]},"institutions":[{"id":"https://openalex.org/I32971472","display_name":"Yale University","ror":"https://ror.org/03v76x132","country_code":"US","type":"education","lineage":["https://openalex.org/I32971472"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Suzhou Yang","raw_affiliation_strings":["Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06520, USA","Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06520, USA","Interdepartmental Neuroscience Program, Yale University, New Haven, CT 0650, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06520, USA","institution_ids":["https://openalex.org/I32971472"]},{"raw_affiliation_string":"Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06520, USA","institution_ids":["https://openalex.org/I32971472"]},{"raw_affiliation_string":"Interdepartmental Neuroscience Program, Yale University, New Haven, CT 0650, USA","institution_ids":["https://openalex.org/I32971472"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5025952029","display_name":"Junjie U. Guo","orcid":"https://orcid.org/0000-0001-8871-0055","observed_orcids":["https://orcid.org/0000-0001-8871-0055"]},"institutions":[{"id":"https://openalex.org/I32971472","display_name":"Yale University","ror":"https://ror.org/03v76x132","country_code":"US","type":"education","lineage":["https://openalex.org/I32971472"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Junjie U. Guo","raw_affiliation_strings":["Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06520, USA","Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06520, USA","Interdepartmental Neuroscience Program, Yale University, New Haven, CT 0650, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06520, USA","institution_ids":["https://openalex.org/I32971472"]},{"raw_affiliation_string":"Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06520, USA","institution_ids":["https://openalex.org/I32971472"]},{"raw_affiliation_string":"Interdepartmental Neuroscience Program, Yale University, New Haven, CT 0650, USA","institution_ids":["https://openalex.org/I32971472"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5025952029"],"corresponding_institution_ids":["https://openalex.org/I32971472"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10604","display_name":"RNA Research and Splicing","score":0.4438000023365021,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10604","display_name":"RNA Research and Splicing","score":0.4438000023365021,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10949","display_name":"Genetic Neurodegenerative Diseases","score":0.2223999947309494,"subfield":{"id":"https://openalex.org/subfields/2804","display_name":"Cellular and Molecular Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10521","display_name":"RNA and protein synthesis mechanisms","score":0.20340000092983246,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/rna-aggregation","display_name":"RNA aggregation","score":0.9800000190734863},{"id":"https://openalex.org/keywords/non-canonical-base-pairs","display_name":"non-canonical base pairs","score":0.8050000071525574},{"id":"https://openalex.org/keywords/repeat-expansion","display_name":"repeat expansion","score":0.5490000247955322},{"id":"https://openalex.org/keywords/hexanucleotide-repeats","display_name":"hexanucleotide repeats","score":0.7210000157356262},{"id":"https://openalex.org/keywords/neurodegeneration","display_name":"neurodegeneration","score":0.7620000243186951},{"id":"https://openalex.org/keywords/rna-binding-proteins","display_name":"RNA-binding proteins","score":0.5429999828338623},{"id":"https://openalex.org/keywords/live-cell-imaging","display_name":"live-cell imaging","score":0.6980000138282776}],"concepts":[{"id":"https://openalex.org/C67705224","wikidata":"https://www.wikidata.org/wiki/Q11053","display_name":"RNA","level":3,"score":0.8127585053443909},{"id":"https://openalex.org/C27149982","wikidata":"https://www.wikidata.org/wiki/Q3456514","display_name":"Tandem repeat","level":4,"score":0.7285283803939819},{"id":"https://openalex.org/C185581394","wikidata":"https://www.wikidata.org/wiki/Q145911","display_name":"Base pair","level":3,"score":0.6189756393432617},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.5466348528862},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.5293589234352112},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.46247804164886475},{"id":"https://openalex.org/C166252455","wikidata":"https://www.wikidata.org/wiki/Q6736610","display_name":"Trinucleotide repeat expansion","level":4,"score":0.432295560836792},{"id":"https://openalex.org/C141231307","wikidata":"https://www.wikidata.org/wiki/Q7020","display_name":"Genome","level":3,"score":0.41437989473342896},{"id":"https://openalex.org/C552990157","wikidata":"https://www.wikidata.org/wiki/Q7430","display_name":"DNA","level":2,"score":0.410054087638855},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.25540095567703247},{"id":"https://openalex.org/C180754005","wikidata":"https://www.wikidata.org/wiki/Q80726","display_name":"Allele","level":3,"score":0.09254619479179382}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1101/2022.04.11.487960","doi":"https://doi.org/10.1101/2022.04.11.487960","is_oa":true,"landing_page_url":"https://doi.org/10.1101/2022.04.11.487960","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2022/04/12/2022.04.11.487960.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.1101/2022.04.11.487960","doi":"https://doi.org/10.1101/2022.04.11.487960","is_oa":true,"landing_page_url":"https://doi.org/10.1101/2022.04.11.487960","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2022/04/12/2022.04.11.487960.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.428600013256073,"id":"https://metadata.un.org/sdg/3"}],"sustainable_development_goals_aurora":[],"study_designs":[],"awards":[],"funders":[{"id":"https://openalex.org/F4320307384","display_name":"New York Stem Cell Foundation","ror":"https://ror.org/03n2a3p06"},{"id":"https://openalex.org/F4320308306","display_name":"Muscular Dystrophy Association","ror":"https://ror.org/01frxsf98"},{"id":"https://openalex.org/F4320332161","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88"}],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W4223607069.pdf","grobid_xml":"https://content.openalex.org/works/W4223607069.grobid-xml"},"referenced_works_count":25,"referenced_works":["https://openalex.org/W2013488820","https://openalex.org/W2013963839","https://openalex.org/W2017237069","https://openalex.org/W2082286833","https://openalex.org/W2099643329","https://openalex.org/W2108763751","https://openalex.org/W2120156669","https://openalex.org/W2125073277","https://openalex.org/W2132573397","https://openalex.org/W2150523249","https://openalex.org/W2154945114","https://openalex.org/W2197459998","https://openalex.org/W2329530882","https://openalex.org/W2520605819","https://openalex.org/W2522261353","https://openalex.org/W2617594926","https://openalex.org/W2780438117","https://openalex.org/W2791482849","https://openalex.org/W2795765276","https://openalex.org/W2891861470","https://openalex.org/W2949082553","https://openalex.org/W3039031062","https://openalex.org/W3081463104","https://openalex.org/W3099595463","https://openalex.org/W4200107600"],"related_works":["https://openalex.org/W2359751344","https://openalex.org/W3031855426","https://openalex.org/W3039686414","https://openalex.org/W2040118711","https://openalex.org/W2266666056","https://openalex.org/W1999617545","https://openalex.org/W1978122417","https://openalex.org/W1964669577","https://openalex.org/W2182086343","https://openalex.org/W4200019550"],"abstract_inverted_index":{"ABSTRACT":[0],"Expansion":[1],"of":[2,20,47,82,106,115,143,158],"short":[3,104],"tandem":[4,63],"repeats":[5],"(STRs)":[6],"in":[7,28],"the":[8,44,74,140,153],"human":[9],"genome":[10],"underlies":[11],"over":[12],"fifty":[13],"genetic":[14],"disorders.":[15],"A":[16],"common":[17],"pathological":[18],"feature":[19],"repeat":[21,48,64,83,127,144,159],"RNAs":[22,84],"is":[23],"their":[24],"propensity":[25],"to":[26,37,59,71],"aggregate":[27],"cells.":[29],"While":[30,102],"these":[31],"RNA":[32,49,78,145,160],"aggregates":[33],"have":[34],"been":[35],"shown":[36],"cause":[38],"toxicity":[39],"by":[40,91,123],"sequestering":[41],"RNA-binding":[42],"proteins,":[43],"molecular":[45,141],"mechanism":[46],"aggregation":[50,87,146],"remains":[51],"unclear.":[52],"Here":[53],"we":[54],"devised":[55],"a":[56,124,136,148],"generalizable":[57,149],"method":[58],"efficiently":[60],"generate":[61],"long":[62],"DNAs":[65],"de":[66],"novo":[67],"and":[68,147,155],"applied":[69],"it":[70],"systematically":[72],"determine":[73],"sequence":[75,154],"features":[76],"underlying":[77],"aggregation.":[79,130],"Live-cell":[80],"imaging":[81],"indicated":[85],"that":[86],"was":[88],"mainly":[89],"driven":[90],"multivalent":[92],"RNA-RNA":[93],"interactions":[94],"via":[95],"either":[96],"canonical":[97],"or":[98],"noncanonical":[99],"base":[100,109,117],"pairs.":[101],"multiple":[103],"runs":[105,114],"two":[107],"consecutive":[108,116],"pairs":[110,118],"were":[111],"sufficient,":[112],"longer":[113],"such":[119],"as":[120],"those":[121],"formed":[122],"neurodegeneration-associated":[125],"hexanucleotide":[126],"further":[128],"enhanced":[129],"In":[131],"summary,":[132],"our":[133],"study":[134],"provides":[135],"unifying":[137],"model":[138],"for":[139,151],"basis":[142],"approach":[150],"identifying":[152],"structural":[156],"determinants":[157],"properties.":[161]},"counts_by_year":[],"updated_date":"2026-08-05T07:39:15.569665","created_date":"2025-10-10T00:00:00"}