{"id":"https://openalex.org/W7204498475","doi":"https://doi.org/10.64898/2026.08.25.747118","title":"Varied forms of mutant tRNA mistranslation produce distinct phenotypes across multiple model organisms","display_name":"Varied forms of mutant tRNA mistranslation produce distinct phenotypes across multiple model organisms","publication_year":2026,"publication_date":"2026-08-27","ids":{"openalex":"https://openalex.org/W7204498475","doi":"https://doi.org/10.64898/2026.08.25.747118"},"language":"en","primary_location":{"id":"doi:10.64898/2026.08.25.747118","doi":"https://doi.org/10.64898/2026.08.25.747118","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.08.25.747118","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/08/27/2026.08.25.747118.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","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.biorxiv.org/content/biorxiv/early/2026/08/27/2026.08.25.747118.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5048755741","display_name":"Brendan Charles","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I125749732","display_name":"Western University","ror":"https://ror.org/02grkyz14","country_code":"CA","type":"education","lineage":["https://openalex.org/I125749732"]}],"countries":["CA"],"is_corresponding":false,"raw_author_name":"Brendan S. Charles","raw_affiliation_strings":["Western University Department of Biology, Western University, London, Ontario, Canada, N6A 5B7"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Western University Department of Biology, Western University, London, Ontario, Canada, N6A 5B7","institution_ids":["https://openalex.org/I125749732"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5005069025","display_name":"Amanda J. Moehring","orcid":"https://orcid.org/0000-0002-8088-4007","observed_orcids":["https://orcid.org/0000-0002-8088-4007"]},"institutions":[{"id":"https://openalex.org/I125749732","display_name":"Western University","ror":"https://ror.org/02grkyz14","country_code":"CA","type":"education","lineage":["https://openalex.org/I125749732"]}],"countries":["CA"],"is_corresponding":true,"raw_author_name":"Amanda J. Moehring","raw_affiliation_strings":["Western University Department of Biology, Western University, London, Ontario, Canada, N6A 5B7"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Western University Department of Biology, Western University, London, Ontario, Canada, N6A 5B7","institution_ids":["https://openalex.org/I125749732"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5005069025"],"corresponding_institution_ids":["https://openalex.org/I125749732"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":1,"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/T10521","display_name":"RNA and protein synthesis mechanisms","score":1.0,"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"}},"topics":[{"id":"https://openalex.org/T10521","display_name":"RNA and protein synthesis mechanisms","score":1.0,"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"}},{"id":"https://openalex.org/T11482","display_name":"RNA modifications and cancer","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"}},{"id":"https://openalex.org/T11764","display_name":"Evolution and Genetic Dynamics","score":0.0,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/translation-errors","display_name":"translation errors","score":0.8960000276565552},{"id":"https://openalex.org/keywords/translational-errors","display_name":"translational errors","score":0.7540000081062317},{"id":"https://openalex.org/keywords/amino-acid-incorporation","display_name":"amino acid incorporation","score":0.7409999966621399},{"id":"https://openalex.org/keywords/toxicity","display_name":"toxicity","score":0.5090000033378601},{"id":"https://openalex.org/keywords/phenotypic-severity","display_name":"phenotypic severity","score":0.5199999809265137},{"id":"https://openalex.org/keywords/drosophila-melanogaster","display_name":"Drosophila melanogaster","score":0.8169999718666077}],"concepts":[{"id":"https://openalex.org/C153957851","wikidata":"https://www.wikidata.org/wiki/Q201448","display_name":"Transfer RNA","level":4,"score":0.8999999761581421},{"id":"https://openalex.org/C143065580","wikidata":"https://www.wikidata.org/wiki/Q3285695","display_name":"Mutant","level":3,"score":0.7825999855995178},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.6675999760627747},{"id":"https://openalex.org/C149364088","wikidata":"https://www.wikidata.org/wiki/Q185917","display_name":"Translation (biology)","level":4,"score":0.6471999883651733},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.6141999959945679},{"id":"https://openalex.org/C515207424","wikidata":"https://www.wikidata.org/wiki/Q8066","display_name":"Amino acid","level":2,"score":0.5224000215530396},{"id":"https://openalex.org/C3675279","wikidata":"https://www.wikidata.org/wiki/Q211935","display_name":"Protein biosynthesis","level":2,"score":0.5127999782562256},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.5037000179290771},{"id":"https://openalex.org/C127716648","wikidata":"https://www.wikidata.org/wiki/Q104053","display_name":"Phenotype","level":3,"score":0.4894999861717224},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.4406000077724457},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.3395000100135803},{"id":"https://openalex.org/C10853874","wikidata":"https://www.wikidata.org/wiki/Q180618","display_name":"Genetic code","level":3,"score":0.3352000117301941},{"id":"https://openalex.org/C2777576037","wikidata":"https://www.wikidata.org/wiki/Q719725","display_name":"Saccharomyces cerevisiae","level":3,"score":0.3091000020503998},{"id":"https://openalex.org/C39685955","wikidata":"https://www.wikidata.org/wiki/Q3455905","display_name":"Translational regulation","level":5,"score":0.2996000051498413},{"id":"https://openalex.org/C19843653","wikidata":"https://www.wikidata.org/wiki/Q213907","display_name":"Model organism","level":3,"score":0.289900004863739},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.288100004196167},{"id":"https://openalex.org/C16318435","wikidata":"https://www.wikidata.org/wiki/Q149299","display_name":"Mutagenesis","level":4,"score":0.2750000059604645},{"id":"https://openalex.org/C21312847","wikidata":"https://www.wikidata.org/wiki/Q7672690","display_name":"T arm","level":5,"score":0.2734000086784363},{"id":"https://openalex.org/C2775992057","wikidata":"https://www.wikidata.org/wiki/Q16956568","display_name":"Translational efficiency","level":5,"score":0.2653000056743622},{"id":"https://openalex.org/C26628138","wikidata":"https://www.wikidata.org/wiki/Q22272147","display_name":"Stringent response","level":4,"score":0.2599000036716461},{"id":"https://openalex.org/C170748874","wikidata":"https://www.wikidata.org/wiki/Q21117977","display_name":"Proofreading","level":4,"score":0.2581000030040741}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.08.25.747118","doi":"https://doi.org/10.64898/2026.08.25.747118","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.08.25.747118","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/08/27/2026.08.25.747118.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:10.64898/2026.08.25.747118","doi":"https://doi.org/10.64898/2026.08.25.747118","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.08.25.747118","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/08/27/2026.08.25.747118.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":[{"score":0.428600013256073,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G2271590008","display_name":null,"funder_award_id":"RGPIN 2020","funder_id":"https://openalex.org/F4320334593","funder_display_name":"Natural Sciences and Engineering Research Council of Canada"},{"id":"https://openalex.org/G8337083222","display_name":null,"funder_award_id":"06464","funder_id":"https://openalex.org/F4320334593","funder_display_name":"Natural Sciences and Engineering Research Council of Canada"}],"funders":[{"id":"https://openalex.org/F4320334392","display_name":"Health Canada","ror":"https://ror.org/05p8nb362"},{"id":"https://openalex.org/F4320334593","display_name":"Natural Sciences and Engineering Research Council of Canada","ror":"https://ror.org/01h531d29"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7204498475.pdf","grobid_xml":"https://content.openalex.org/works/W7204498475.grobid-xml"},"referenced_works_count":46,"referenced_works":["https://openalex.org/W1539868719","https://openalex.org/W1548166250","https://openalex.org/W1923250545","https://openalex.org/W1956613997","https://openalex.org/W1966840835","https://openalex.org/W1970563053","https://openalex.org/W1972773471","https://openalex.org/W1984512854","https://openalex.org/W1997401532","https://openalex.org/W2017411951","https://openalex.org/W2025390294","https://openalex.org/W2039645753","https://openalex.org/W2039702442","https://openalex.org/W2044573154","https://openalex.org/W2066392481","https://openalex.org/W2068628419","https://openalex.org/W2140425855","https://openalex.org/W2143210482","https://openalex.org/W2152231829","https://openalex.org/W2164004777","https://openalex.org/W2288549395","https://openalex.org/W2418276263","https://openalex.org/W2515680332","https://openalex.org/W2620574740","https://openalex.org/W2760281524","https://openalex.org/W2858571940","https://openalex.org/W2904427364","https://openalex.org/W2939643004","https://openalex.org/W2954605289","https://openalex.org/W3084221411","https://openalex.org/W3175333884","https://openalex.org/W3194108781","https://openalex.org/W3209378792","https://openalex.org/W3209383543","https://openalex.org/W4213116524","https://openalex.org/W4220948360","https://openalex.org/W4223487635","https://openalex.org/W4224257426","https://openalex.org/W4315752688","https://openalex.org/W4372333536","https://openalex.org/W4387215274","https://openalex.org/W4389669882","https://openalex.org/W4390663488","https://openalex.org/W4402745861","https://openalex.org/W4410419054","https://openalex.org/W4417117792"],"related_works":["https://openalex.org/W7047585460","https://openalex.org/W3021522857","https://openalex.org/W4402745861","https://openalex.org/W4220948360","https://openalex.org/W3175333884","https://openalex.org/W4417457875","https://openalex.org/W2971460580","https://openalex.org/W4280565827","https://openalex.org/W4416938562","https://openalex.org/W2909180002"],"abstract_inverted_index":{"Abstract":[0],"Mutant":[1],"tRNA":[2,10,34,87,95,182,193,204,230],"mistranslation":[3,35,126,157],"is":[4],"a":[5,82,162],"phenomenon":[6],"in":[7,116,184],"which":[8,91],"specific":[9],"gene":[11],"mutations":[12],"cause":[13],"translational":[14],"errors":[15],"wherein":[16],"amino":[17,67,121],"acids":[18],"incorporated":[19],"during":[20],"translation":[21],"differ":[22],"from":[23,109,149],"those":[24],"coded":[25],"by":[26],"mRNA":[27],"sequences.":[28],"The":[29],"biological":[30,242],"consequences":[31],"of":[32,56,64,70,73,86,93,100,138,156,167,172,179,189,200,223,240,247],"mutant":[33,59,110,180],"are":[36,42,50,97,133],"highly":[37],"complex":[38],"and":[39,76,170,198,235,244],"contextual,":[40],"but":[41],"often":[43,107],"deleterious.":[44],"Importantly,":[45,131],"many":[46],"variables":[47],"exist":[48],"that":[49,105,112,127,144,216],"likely":[51],"to":[52,89,136],"affect":[53],"the":[54,65,214],"outcomes":[55,243],"any":[57],"one":[58],"mistranslating":[60,94,181,192,203,229],"tRNA;":[61],"biochemical":[62,117],"characteristics":[63,92],"exchanged":[66,120],"acids,":[68,122],"frequency":[69,191,202],"use,":[71],"identity":[72],"mistranslated":[74,168],"products,":[75],"so":[77],"on.":[78],"Here,":[79],"we":[80],"generate":[81],"carefully":[83],"curated":[84],"array":[85],"mutants":[88],"assess":[90],"variants":[96,194,205],"most":[98],"predictive":[99],"deleterious":[101],"phenotypes.":[102,174,210],"We":[103],"find":[104],"toxicity":[106],"arises":[108],"tRNAs":[111],"induce":[113],"dramatic":[114],"changes":[115],"properties":[118],"between":[119,165],"as":[123,125],"well":[124],"occurs":[128],"more":[129,150],"frequently.":[130],"exceptions":[132],"also":[134],"observed":[135],"each":[137,228],"these":[139],"general":[140,218],"rules,":[141],"implying":[142],"instead":[143],"some":[145],"deliriousness":[146],"may":[147,220],"arise":[148],"granular,":[151],"product-specific":[152],"mechanisms.":[153],"Additionally,":[154],"quantification":[155],"via":[158],"mass":[159],"spectrometry":[160],"demonstrates":[161],"weak":[163],"relationship":[164],"quantity":[166],"products":[169],"severity":[171],"toxic":[173],"Lastly,":[175],"despite":[176],"previous":[177],"establishment":[178],"models":[183],"Drosophila":[185],"melanogaster":[186],",":[187],"incorporation":[188,199],"higher":[190],"was":[195],"largely":[196],"unsuccessful,":[197],"lower":[201],"produces":[206],"no":[207],"detectable":[208],"developmental":[209],"These":[211],"experiments":[212],"support":[213],"notion":[215],"although":[217],"rules":[219],"be":[221],"capable":[222],"reasonably":[224],"predicting":[225],"their":[226],"consequences,":[227],"variant":[231],"warrants":[232],"individual":[233],"consideration":[234],"investigation":[236],"for":[237],"thorough":[238],"understanding":[239],"its":[241],"precise":[245],"mechanisms":[246],"toxicity.":[248]},"counts_by_year":[{"year":2026,"cited_by_count":1}],"updated_date":"2026-11-08T12:12:28.789561","created_date":"2026-08-28T00:00:00"}