{"id":"https://openalex.org/W2979548526","doi":null,"title":"Genetic Rescue of Fragile X Syndrome Links FMRP Deficiency to Codon Optimality-Dependent RNA Destabilization [preprint]","display_name":"Genetic Rescue of Fragile X Syndrome Links FMRP Deficiency to Codon Optimality-Dependent RNA Destabilization [preprint]","publication_year":2019,"publication_date":"2019-10-10","ids":{"openalex":"https://openalex.org/W2979548526","mag":"2979548526"},"language":"en","primary_location":{"id":"pmh:oai:escholarship.umassmed.edu:faculty_pubs-2653","doi":null,"is_oa":true,"landing_page_url":"https://escholarship.umassmed.edu/faculty_pubs/1641","pdf_url":null,"source":{"id":"https://openalex.org/S4306400883","display_name":"The Journal of the American Medical Association (JAMA) Network (American Medical Association)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I173654999","host_organization_name":"American Medical Association","host_organization_lineage":["https://openalex.org/I173654999"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"University of Massachusetts Medical School Faculty Publications","raw_type":"text"},"volume":null,"type":"article","is_traditional":true,"indexed_in":[],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://escholarship.umassmed.edu/faculty_pubs/1641","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5004223504","display_name":"Huan Shu","orcid":"https://orcid.org/0000-0002-3395-2409","observed_orcids":["https://orcid.org/0000-0002-3395-2409"]},"institutions":[{"id":"https://openalex.org/I166722992","display_name":"University of Massachusetts Chan Medical School","ror":"https://ror.org/0464eyp60","country_code":"US","type":"education","lineage":["https://openalex.org/I166722992"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Shu, Huan","raw_affiliation_strings":["Program in Molecular Medicine, University of Massachusetts Medical School Worcester"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Program in Molecular Medicine, University of Massachusetts Medical School Worcester","institution_ids":["https://openalex.org/I166722992"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5059970061","display_name":"Elisa R. Donnard","orcid":"https://orcid.org/0000-0002-8834-8110","observed_orcids":["https://orcid.org/0000-0002-8834-8110"]},"institutions":[{"id":"https://openalex.org/I166722992","display_name":"University of Massachusetts Chan Medical School","ror":"https://ror.org/0464eyp60","country_code":"US","type":"education","lineage":["https://openalex.org/I166722992"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Donnard, Elisa","raw_affiliation_strings":["Bioinformatics and Integrative Biology, University of Massachusetts Medical School Worcester"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Bioinformatics and Integrative Biology, University of Massachusetts Medical School Worcester","institution_ids":["https://openalex.org/I166722992"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5107840865","display_name":"Botao Liu","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I166722992","display_name":"University of Massachusetts Chan Medical School","ror":"https://ror.org/0464eyp60","country_code":"US","type":"education","lineage":["https://openalex.org/I166722992"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Liu, Botao","raw_affiliation_strings":["Program in Molecular Medicine, University of Massachusetts Medical School Worcester"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Program in Molecular Medicine, University of Massachusetts Medical School Worcester","institution_ids":["https://openalex.org/I166722992"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5042061460","display_name":"Joel D. Richter","orcid":"https://orcid.org/0000-0003-2753-2501","observed_orcids":["https://orcid.org/0000-0003-2753-2501"]},"institutions":[{"id":"https://openalex.org/I166722992","display_name":"University of Massachusetts Chan Medical School","ror":"https://ror.org/0464eyp60","country_code":"US","type":"education","lineage":["https://openalex.org/I166722992"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Richter, Joel D.","raw_affiliation_strings":["Program in Molecular Medicine, University of Massachusetts Medical School Worcester"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Program in Molecular Medicine, University of Massachusetts Medical School Worcester","institution_ids":["https://openalex.org/I166722992"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I166722992"],"apc_list":null,"apc_paid":null,"fwci":0.2551,"has_fulltext":false,"cited_by_count":2,"citation_normalized_percentile":{"value":0.50029581,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":88,"max":93},"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/T11772","display_name":"Genetics and Neurodevelopmental Disorders","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"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/T11772","display_name":"Genetics and Neurodevelopmental Disorders","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"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/T10521","display_name":"RNA and protein synthesis mechanisms","score":0.0003000000142492354,"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/T10604","display_name":"RNA Research and Splicing","score":0.0,"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/fragile-x-syndrome","display_name":"fragile X syndrome","score":0.9990000128746033},{"id":"https://openalex.org/keywords/fmrp","display_name":"FMRP","score":0.9589999914169312},{"id":"https://openalex.org/keywords/cpeb1","display_name":"CPEB1","score":0.7250000238418579},{"id":"https://openalex.org/keywords/genetic-rescue","display_name":"genetic rescue","score":0.7459999918937683},{"id":"https://openalex.org/keywords/codon-optimality","display_name":"codon optimality","score":0.8069999814033508},{"id":"https://openalex.org/keywords/rna-destabilization","display_name":"RNA destabilization","score":0.8899999856948853},{"id":"https://openalex.org/keywords/rna-degradation","display_name":"RNA degradation","score":0.6890000104904175},{"id":"https://openalex.org/keywords/ribosome-occupancy","display_name":"ribosome occupancy","score":0.9440000057220459},{"id":"https://openalex.org/keywords/protein-synthesis-inhibition","display_name":"protein synthesis inhibition","score":0.6729999780654907},{"id":"https://openalex.org/keywords/cortical-neurons","display_name":"cortical neurons","score":0.7950000166893005},{"id":"https://openalex.org/keywords/fmr1-knockout-mice","display_name":"Fmr1 knockout mice","score":0.6620000004768372}],"concepts":[{"id":"https://openalex.org/C2779063550","wikidata":"https://www.wikidata.org/wiki/Q905435","display_name":"FMR1","level":4,"score":0.7610409259796143},{"id":"https://openalex.org/C2777630245","wikidata":"https://www.wikidata.org/wiki/Q221472","display_name":"Fragile X syndrome","level":2,"score":0.671933650970459},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.6647862195968628},{"id":"https://openalex.org/C67705224","wikidata":"https://www.wikidata.org/wiki/Q11053","display_name":"RNA","level":3,"score":0.6224158406257629},{"id":"https://openalex.org/C182325514","wikidata":"https://www.wikidata.org/wiki/Q7322425","display_name":"Ribosome profiling","level":5,"score":0.572731614112854},{"id":"https://openalex.org/C162317418","wikidata":"https://www.wikidata.org/wiki/Q252857","display_name":"Transcriptome","level":4,"score":0.5456150770187378},{"id":"https://openalex.org/C149364088","wikidata":"https://www.wikidata.org/wiki/Q185917","display_name":"Translation (biology)","level":4,"score":0.5359445810317993},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.5111964344978333},{"id":"https://openalex.org/C105580179","wikidata":"https://www.wikidata.org/wiki/Q188928","display_name":"Messenger RNA","level":3,"score":0.48285824060440063},{"id":"https://openalex.org/C88478588","wikidata":"https://www.wikidata.org/wiki/Q42244","display_name":"Ribosome","level":4,"score":0.4633368253707886},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.44395917654037476},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.4209766089916229},{"id":"https://openalex.org/C150194340","wikidata":"https://www.wikidata.org/wiki/Q26972","display_name":"Gene expression","level":3,"score":0.3501307964324951},{"id":"https://openalex.org/C3020422209","wikidata":"https://www.wikidata.org/wiki/Q221472","display_name":"Fragile x","level":3,"score":0.22093543410301208}],"mesh":[],"locations_count":1,"locations":[{"id":"pmh:oai:escholarship.umassmed.edu:faculty_pubs-2653","doi":null,"is_oa":true,"landing_page_url":"https://escholarship.umassmed.edu/faculty_pubs/1641","pdf_url":null,"source":{"id":"https://openalex.org/S4306400883","display_name":"The Journal of the American Medical Association (JAMA) Network (American Medical Association)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I173654999","host_organization_name":"American Medical Association","host_organization_lineage":["https://openalex.org/I173654999"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"University of Massachusetts Medical School Faculty Publications","raw_type":"text"}],"best_oa_location":{"id":"pmh:oai:escholarship.umassmed.edu:faculty_pubs-2653","doi":null,"is_oa":true,"landing_page_url":"https://escholarship.umassmed.edu/faculty_pubs/1641","pdf_url":null,"source":{"id":"https://openalex.org/S4306400883","display_name":"The Journal of the American Medical Association (JAMA) Network (American Medical Association)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I173654999","host_organization_name":"American Medical Association","host_organization_lineage":["https://openalex.org/I173654999"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"University of Massachusetts Medical School Faculty Publications","raw_type":"text"},"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.6240000128746033}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":67,"referenced_works":["https://openalex.org/W1168435588","https://openalex.org/W1521067743","https://openalex.org/W1630550847","https://openalex.org/W1906706885","https://openalex.org/W1936641192","https://openalex.org/W1945157585","https://openalex.org/W1965456948","https://openalex.org/W1966778471","https://openalex.org/W1983788160","https://openalex.org/W1999574084","https://openalex.org/W2002780348","https://openalex.org/W2013321787","https://openalex.org/W2017557491","https://openalex.org/W2018590530","https://openalex.org/W2036897871","https://openalex.org/W2037437212","https://openalex.org/W2052326665","https://openalex.org/W2053003053","https://openalex.org/W2068065584","https://openalex.org/W2081470277","https://openalex.org/W2084889756","https://openalex.org/W2086157203","https://openalex.org/W2096476959","https://openalex.org/W2096821445","https://openalex.org/W2099545905","https://openalex.org/W2112313787","https://openalex.org/W2115452664","https://openalex.org/W2116276594","https://openalex.org/W2123824748","https://openalex.org/W2130431667","https://openalex.org/W2132943956","https://openalex.org/W2134045916","https://openalex.org/W2134063049","https://openalex.org/W2140729960","https://openalex.org/W2140951250","https://openalex.org/W2146512944","https://openalex.org/W2147609603","https://openalex.org/W2153114644","https://openalex.org/W2154391980","https://openalex.org/W2158323020","https://openalex.org/W2169353806","https://openalex.org/W2169589032","https://openalex.org/W2170551349","https://openalex.org/W2179438025","https://openalex.org/W2237226910","https://openalex.org/W2298977477","https://openalex.org/W2319914265","https://openalex.org/W2495238549","https://openalex.org/W2520264800","https://openalex.org/W2529467471","https://openalex.org/W2541158021","https://openalex.org/W2554008396","https://openalex.org/W2588514930","https://openalex.org/W2744596343","https://openalex.org/W2745668358","https://openalex.org/W2759506905","https://openalex.org/W2797218669","https://openalex.org/W2885321095","https://openalex.org/W2886042183","https://openalex.org/W2898814165","https://openalex.org/W2940525406","https://openalex.org/W2948566502","https://openalex.org/W2950430276","https://openalex.org/W2950910720","https://openalex.org/W2994774550","https://openalex.org/W3046003662","https://openalex.org/W3106057438"],"related_works":["https://openalex.org/W7019237172","https://openalex.org/W3106273223","https://openalex.org/W2237226910","https://openalex.org/W3159650156","https://openalex.org/W1991476271","https://openalex.org/W2797244528","https://openalex.org/W7125273501","https://openalex.org/W4391642175","https://openalex.org/W2766602515","https://openalex.org/W2098756736"],"abstract_inverted_index":{"Fragile":[0],"X":[1],"syndrome":[2],"(FXS)":[3],"is":[4,226],"caused":[5],"by":[6,107,229],"inactivation":[7],"of":[8,13,26,36,45,66,88,103,156,165,182,185,194,210,220,233],"FMR1":[9],"gene":[10],"and":[11,74,86,101,118,131,145,215],"loss":[12,193],"its":[14,27,75],"encoded":[15],"product":[16],"the":[17,31,58,92,98,113,183,208,221,230,234],"RNA":[18,67,89,157,166,175,201,216],"binding":[19,129],"protein":[20],"FMRP,":[21],"which":[22,47,205],"generally":[23],"represses":[24],"translation":[25,104],"target":[28],"transcripts":[29],"in":[30,69,80,112,120,142,148,168,190,203],"brain.":[32,114,151],"In":[33],"mouse":[34],"models":[35,123],"FXS":[37],"(i.e.,":[38],"Fmr1":[39,42,70],"knockout":[40],"animals;":[41],"KO),":[43],"deletion":[44],"Cpeb1,":[46],"encodes":[48],"a":[49,161,179,199],"translational":[50],"activator,":[51],"mitigates":[52],"nearly":[53],"all":[54],"pathophysiologies":[55],"associated":[56],"with":[57],"disorder.":[59,235],"Here":[60],"we":[61],"reveal":[62],"unexpected":[63],"wide-spread":[64],"dys-regulation":[65,100],"abundance":[68],"KO":[71,83],"brain":[72],"cortex":[73],"rescue":[76,102,232],"to":[77,178],"normal":[78],"levels":[79,90],"Fmr1/Cpeb1":[81],"double":[82],"mice.":[84],"Alteration":[85],"restoration":[87],"are":[91,124],"dominant":[93],"molecular":[94],"events":[95,225],"that":[96,137],"drive":[97],"observed":[99],"as":[105],"measured":[106],"whole":[108,153],"transcriptome":[109,154],"ribosome":[110,213],"occupany":[111],"The":[115],"RNAs":[116],"down-regulated":[117],"rescued":[119],"these":[121,224],"animal":[122],"highly":[125],"enriched":[126],"for":[127],"FMRP":[128,149,169],"targets":[130],"have":[132],"an":[133],"optimal":[134],"codon":[135,162,211],"bias":[136],"would":[138],"predict":[139],"their":[140],"stability":[141],"wild":[143],"type":[144],"possible":[146],"instability":[147,202],"knock-out":[150,170],"Indeed,":[152],"analysis":[155],"metabolic":[158],"rates":[159],"demonstrates":[160],"optimality-dependent":[163],"elevation":[164],"destruction":[167,176],"cortical":[171],"neurons.":[172],"This":[173],"elevated":[174],"leads":[177],"massive":[180],"reshuffling":[181],"identities":[184],"stabilizing":[186],"versus":[187],"destabilizing":[188],"codons":[189],"neurons":[191],"upon":[192],"FMRP.":[195],"Our":[196],"results":[197,206],"show":[198],"widespread":[200],"FXS,":[204],"from":[207],"uncoupling":[209],"optimality,":[212],"occupancy,":[214],"degradation":[217],"mechanisms.":[218],"Re-establishment":[219],"linkage":[222],"among":[223],"likely":[227],"required":[228],"genetic":[231]},"counts_by_year":[{"year":2022,"cited_by_count":1},{"year":2020,"cited_by_count":1}],"updated_date":"2026-11-03T10:50:19.383937","created_date":"2019-10-18T00:00:00"}
