Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.18/2705
Título: Translation of the human erythropoietin transcript is regulated by an upstream open reading frame in response to hypoxia
Autor: Barbosa, Cristina
Romão, Luísa
Palavras-chave: eIF2α
Erythropoietin (EPO)
Hypoxia
Phosphorylation
Translational Regulation
Upstream Open Reading Frame (uORF)
RNA
Doenças Genéticas
Data: 19-Mar-2014
Editora: Cold Spring Harbor Laboratory Press/ RNA Society
Citação: RNA. 2014 May;20(5):594-608. doi: 10.1261/rna.040915.113. Epub 2014 Mar 19
Resumo: Erythropoietin (EPO) is a key mediator hormone for hypoxic induction of erythropoiesis that also plays important nonhematopoietic functions. It has been shown that EPO gene expression regulation occurs at different levels, including transcription and mRNA stabilization. In this report, we show that expression of EPO is also regulated at the translational level by an upstream open reading frame (uORF) of 14 codons. As judged by comparisons of protein and mRNA levels, the uORF acts as a cis-acting element that represses translation of the main EPO ORF in unstressed HEK293, HepG2, and HeLa cells. However, in response to hypoxia, this repression is significantly released, specifically in HeLa cells, through a mechanism that involves processive scanning of ribosomes from the 5' end of the EPO transcript and enhanced ribosome bypass of the uORF. In addition, we demonstrate that in HeLa cells, hypoxia induces the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) concomitantly with a significant increase of EPO protein synthesis. These findings provide a framework for understanding that production of high levels of EPO induced by hypoxia also involves regulation at the translational level.
Peer review: yes
URI: http://hdl.handle.net/10400.18/2705
DOI: 10.1261/rna.040915.113
ISSN: 1355-8382
Versão do Editor: http://rnajournal.cshlp.org/content/20/5/594.abstract
Aparece nas colecções:DGH - Artigos em revistas internacionais

Ficheiros deste registo:
Ficheiro Descrição TamanhoFormato 
Barbosa Romão 2014.pdf1,1 MBAdobe PDFVer/Abrir    Acesso Restrito. Solicitar cópia ao autor!


FacebookTwitterDeliciousLinkedInDiggGoogle BookmarksMySpace
Formato BibTex MendeleyEndnote Degois 

Todos os registos no repositório estão protegidos por leis de copyright, com todos os direitos reservados.