Please use this identifier to cite or link to this item: http://hdl.handle.net/10773/27448
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dc.contributor.authorVaranda, Ana Sofiapt_PT
dc.contributor.authorSantos, Mafaldapt_PT
dc.contributor.authorSoares, Ana R.pt_PT
dc.contributor.authorVitorino, Ruipt_PT
dc.contributor.authorOliveira, Patríciapt_PT
dc.contributor.authorOliveira, Carlapt_PT
dc.contributor.authorSantos, Manuel A. S.pt_PT
dc.date.accessioned2020-01-31T17:55:12Z-
dc.date.available2020-01-31T17:55:12Z-
dc.date.issued2020-
dc.identifier.issn1547-6286pt_PT
dc.identifier.urihttp://hdl.handle.net/10773/27448-
dc.description.abstractDeregulation of tRNAs, aminoacyl-tRNA synthetases (aaRS) or tRNA modifying enzymes, increase the level of protein synthesis errors (PSE) and are associated with several diseases, but the cause-effect mechanisms of these pathologies remain elusive. To clarify the role of PSE in human biology, we have engineered a HEK293 cell line to overexpress a wild type (Wt) tRNASer and two tRNASer mutants that misincorporate serine at non-cognate codon sites. Then, we followed long-term adaptation to PSE of such recombinant cells by analysing cell viability, protein synthesis rate and activation of protein quality control mechanisms (PQC). Engineered cells showed higher level of misfolded and aggregated proteins; activated the ubiquitin-proteasome system (UPS) and the unfolded protein response (UPR), indicative of proteotoxic stress. Adaptation to PSE involved increased protein turnover, UPR up-regulation and altered protein synthesis rate. Gene expression analysis showed that engineered cells presented recurrent alterations in the endoplasmic reticulum, cell adhesion and calcium homeostasis. Herein, we unveil new phenotypic consequences of protein synthesis errors in human cells and identify the protein quality control processes that are necessary for long-term adaptation to PSE and proteotoxic stress. Our data provide important insight on how chronic proteotoxic stress may cause disease and highlight potential biological pathways that support the association of PSE with disease.pt_PT
dc.language.isoengpt_PT
dc.publisherTaylor & Francispt_PT
dc.relationPOCI-01-0145-FEDER -007274pt_PT
dc.relationinfo:eu-repo/grantAgreement/FCT/COMPETE/132983/PTpt_PT
dc.relationNORTE-01-0145-FEDER-000029pt_PT
dc.relationinfo:eu-repo/grantAgreement/FCT/5876/147343/PTpt_PT
dc.relationPOCI-01-0145-FEDER-007628pt_PT
dc.relationCENTRO-01-0145-FEDER-000003pt_PT
dc.relationPOCI-01- 0145-FEDER-016428pt_PT
dc.relationinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F91020%2F2012/PTpt_PT
dc.relationSFRH/BD/76417/2011pt_PT
dc.relationPOCI-01-0145-FEDER-028834pt_PT
dc.relationPTDC/BiAMiB/31238/2017pt_PT
dc.relationinfo:eu-repo/grantAgreement/FCT/COMPETE/132983/PTpt_PT
dc.relationPTDC/BIMMEC/1719/2014pt_PT
dc.relationPTDC/BEXBCM/2121/2014pt_PT
dc.relationinfo:eu-repo/grantAgreement/FCT/5876/147343/PTpt_PT
dc.relationPOCI-01-0145-FEDER-007628pt_PT
dc.relationNORTE-01-0145-FEDER-000029pt_PT
dc.relationPOCI-01-0145-FEDER-007274pt_PT
dc.relationCENTRO-01-0145-FEDER-000003pt_PT
dc.rightsrestrictedAccesspt_PT
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectProtein synthesis errorspt_PT
dc.subjecttRNAspt_PT
dc.subjectProtein quality controlpt_PT
dc.subjectUbiquitin-proteasome systempt_PT
dc.subjectUnfolded protein responsept_PT
dc.subjectHuman cellspt_PT
dc.subjectProteostasispt_PT
dc.subjectProtein synthesis errorspt_PT
dc.subjectMistranslationpt_PT
dc.titleHuman cells adapt to translational errors by modulating protein synthesis rate and protein turnoverpt_PT
dc.typearticlept_PT
dc.description.versionpublishedpt_PT
dc.peerreviewedyespt_PT
degois.publication.firstPage135pt_PT
degois.publication.issue1pt_PT
degois.publication.lastPage149pt_PT
degois.publication.titleRNA Biologypt_PT
degois.publication.volume17pt_PT
dc.identifier.doi10.1080/15476286.2019.1670039pt_PT
dc.identifier.essn1555-8584pt_PT
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