Publication
Regulation of the human erythropoietin expression via an upstream open reading frame in cardiac tissue
| dc.contributor.author | Onofre, Cláudia | |
| dc.contributor.author | Ferrão, José | |
| dc.contributor.author | Barbosa, Cristina | |
| dc.contributor.author | Romão, Luísa | |
| dc.date.accessioned | 2017-03-03T19:02:10Z | |
| dc.date.embargo | 2025 | |
| dc.date.issued | 2016-11 | |
| dc.description.abstract | 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 mRNA translation initiation and is mediated via different cis-acting elements present in the mRNA 5’ untranslated region (5’UTR); these elements include upstream open reading frames (uORFs). uORFs modulate translation of the main ORF by decreasing the number and/or efficiency of scanning ribosomes to reinitiate at the start codon of the main ORF. In its classical hormonal role, human erythropoietin (EPO) is a glycoprotein synthesized and released mainly from the kidney, which has a key role in hematopoiesis. However, recent studies have revealed that EPO is a multifunctional molecule produced and utilized by many tissues that rapidly responds to different cell stress stimuli and tissue injuries. The 5’UTR sequence of the human EPO mRNA has one uORF with 14 codons, which is conserved among different species, indicating its potential role in translational regulation. Indeed, we have recently shown that translation of human EPO mRNA is regulated by its uORF in response to hypoxia in HeLa cells [Barbosa & Romão (2014). RNA. 20(5):594-608]. 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 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. We are currently exploring additional mechanisms through which EPO cardioprotection effects are regulated at the translational level. | pt_PT |
| dc.description.version | N/A | pt_PT |
| dc.identifier.uri | http://hdl.handle.net/10400.18/4478 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc/4.0/ | pt_PT |
| dc.subject | Genómica Funcional e Estrutural | pt_PT |
| dc.subject | Expressão Génica | pt_PT |
| dc.subject | Eritropoietina | pt_PT |
| dc.title | Regulation of the human erythropoietin expression via an upstream open reading frame in cardiac tissue | pt_PT |
| dc.type | conference object | |
| dspace.entity.type | Publication | |
| oaire.citation.conferencePlace | Coimbra, Portugal | pt_PT |
| oaire.citation.title | 20ª Reunião anual da Sociedade Portuguesa de Genética Humana, 10-12 novembro 2016 | pt_PT |
| rcaap.rights | embargoedAccess | pt_PT |
| rcaap.type | conferenceObject | pt_PT |