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Translational control of the human erythropoietin via an upstream open reading frame in cardiac and muscle tissue

2015-09-09Conference object Restricted access
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dc.contributor.authorOnofre, Claudia
dc.contributor.authorBarbosa, Cristina
dc.contributor.authorRomão, Luísa
dc.date.accessioned2016-03-04T16:53:38Z
dc.date.available2020-12-31T01:30:10Z
dc.date.issued2015-09-09
dc.description.abstractBeyond its well-known hematopoietic action, erythropoietin (EPO) has diverse cellular effects in non-hematopoietic tissues. For example, in cases of tissue injury, such as cardiac ischemia or acute myocardial infarct, EPO expression increases locally, providing a cardioprotective effect. Cellular stress activates an integrated stress response, which includes rapid changes in global and gene-specific translation. Translational regulation of specific transcripts mostly occurs at translation initiation and is mediated via different cis-acting elements, including upstream open reading frames (uORFs). The human EPO 5’ untranslated region (5’UTR) has one uORF with 14 codons that is conserved among different species, indicating its potential regulatory role. To test whether EPO expression is translationally regulated in response to ischemia in cardiac tissue, reporter constructs containing the normal or mutant EPO 5’UTR fused to the Firefly luciferase cistron were expressed in H9c2 (heart/myocardium myoblasts) and C2C12 (muscle myoblasts) cell lines. Luminometry assays revealed that the EPO uORF represses translation of the main ORF at about 60-70%, in both cell lines. Under chemical ischemia, EPO uORF-mediated translation repression is specifically released in muscle cells. In response to hypoxia, translational derepression occurs in both cell lines. Although the eIF2-alpha phosphorylation occurs in both conditions, thapsigargin treatment does not affect EPO translation. We are currently exploring additional mechanisms through which EPO cardioprotection effects are regulated at the translational level.pt_PT
dc.description.sponsorshipThis research was supported by Fundação para a Ciência e a Tecnologia – FCT (PTDC/BIM-MED/0352/2012) and Instituto Nacional de Saúde Doutor Ricardo Jorge.pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.18/3660
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.subjectGenómica Funcional e Estruturalpt_PT
dc.subjectExpressão Génicapt_PT
dc.subjectSíntese Proteicapt_PT
dc.titleTranslational control of the human erythropoietin via an upstream open reading frame in cardiac and muscle tissuept_PT
dc.typeconference object
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBIM-MED%2F0352%2F2012/PT
oaire.citation.conferencePlaceHeidelberg, Alemanhapt_PT
oaire.citation.titleEMBO Conference Protein Synthesis and Translational Control (EMBO), European Molecular Biology Laboratory, 9-13 September 2015pt_PT
oaire.fundingStream3599-PPCDT
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typeconferenceObjectpt_PT
relation.isProjectOfPublication66f861e5-7176-4c26-8a4e-70cc7f66684e
relation.isProjectOfPublication.latestForDiscovery66f861e5-7176-4c26-8a4e-70cc7f66684e

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