Expression of human Hemojuvelin (HJV) is tightly regulated by two upstream open reading frames in HJV mRNA that respond to iron overload in hepatic cells

Detalhes bibliográficos
Autor(a) principal: Onofre, Claudia
Data de Publicação: 2015
Outros Autores: Tomé, Filipa, Barbosa, Cristina, Silva, Ana Luísa, Romão, Luísa
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.18/3345
Resumo: Acessível em: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372701/
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spelling Expression of human Hemojuvelin (HJV) is tightly regulated by two upstream open reading frames in HJV mRNA that respond to iron overload in hepatic cellsExpressão GénicaHemojuvelinaGenómica Funcional e EstruturalAcessível em: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372701/The gene encoding human hemojuvelin (HJV) is one of the genes that, when mutated, can cause juvenile hemochromatosis, an early-onset inherited disorder associated with iron overload. The 5' untranslated region of the human HJV mRNA has two upstream open reading frames (uORFs), with 28 and 19 codons formed by two upstream AUGs (uAUGs) sharing the same in-frame stop codon. Here we show that these uORFs decrease the translational efficiency of the downstream main ORF in HeLa and HepG2 cells. Indeed, ribosomal access to the main AUG is conditioned by the strong uAUG context, which results in the first uORF being translated most frequently. The reach of the main ORF is then achieved by ribosomes that resume scanning after uORF translation. Furthermore, the amino acid sequences of the uORF-encoded peptides also reinforce the translational repression of the main ORF. Interestingly, when iron levels increase, translational repression is relieved specifically in hepatic cells. The upregulation of protein levels occurs along with phosphorylation of the eukaryotic initiation factor 2α. Nevertheless, our results support a model in which the increasing recognition of the main AUG is mediated by a tissue-specific factor that promotes uORF bypass. These results support a tight HJV translational regulation involved in iron homeostasis.American Society for MicrobiologyRepositório Científico do Instituto Nacional de SaúdeOnofre, ClaudiaTomé, FilipaBarbosa, CristinaSilva, Ana LuísaRomão, Luísa2016-02-16T17:05:46Z2015-042015-04-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/3345engMol Cell Biol. 2015 Apr;35(8):1376-89. doi: 10.1128/MCB.01462-14. Epub 2015 Feb 9.0270-730610.1128/MCB.01462-14info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-20T15:39:46Zoai:repositorio.insa.pt:10400.18/3345Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:38:17.532954Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Expression of human Hemojuvelin (HJV) is tightly regulated by two upstream open reading frames in HJV mRNA that respond to iron overload in hepatic cells
title Expression of human Hemojuvelin (HJV) is tightly regulated by two upstream open reading frames in HJV mRNA that respond to iron overload in hepatic cells
spellingShingle Expression of human Hemojuvelin (HJV) is tightly regulated by two upstream open reading frames in HJV mRNA that respond to iron overload in hepatic cells
Onofre, Claudia
Expressão Génica
Hemojuvelina
Genómica Funcional e Estrutural
title_short Expression of human Hemojuvelin (HJV) is tightly regulated by two upstream open reading frames in HJV mRNA that respond to iron overload in hepatic cells
title_full Expression of human Hemojuvelin (HJV) is tightly regulated by two upstream open reading frames in HJV mRNA that respond to iron overload in hepatic cells
title_fullStr Expression of human Hemojuvelin (HJV) is tightly regulated by two upstream open reading frames in HJV mRNA that respond to iron overload in hepatic cells
title_full_unstemmed Expression of human Hemojuvelin (HJV) is tightly regulated by two upstream open reading frames in HJV mRNA that respond to iron overload in hepatic cells
title_sort Expression of human Hemojuvelin (HJV) is tightly regulated by two upstream open reading frames in HJV mRNA that respond to iron overload in hepatic cells
author Onofre, Claudia
author_facet Onofre, Claudia
Tomé, Filipa
Barbosa, Cristina
Silva, Ana Luísa
Romão, Luísa
author_role author
author2 Tomé, Filipa
Barbosa, Cristina
Silva, Ana Luísa
Romão, Luísa
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Repositório Científico do Instituto Nacional de Saúde
dc.contributor.author.fl_str_mv Onofre, Claudia
Tomé, Filipa
Barbosa, Cristina
Silva, Ana Luísa
Romão, Luísa
dc.subject.por.fl_str_mv Expressão Génica
Hemojuvelina
Genómica Funcional e Estrutural
topic Expressão Génica
Hemojuvelina
Genómica Funcional e Estrutural
description Acessível em: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372701/
publishDate 2015
dc.date.none.fl_str_mv 2015-04
2015-04-01T00:00:00Z
2016-02-16T17:05:46Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.18/3345
url http://hdl.handle.net/10400.18/3345
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Mol Cell Biol. 2015 Apr;35(8):1376-89. doi: 10.1128/MCB.01462-14. Epub 2015 Feb 9.
0270-7306
10.1128/MCB.01462-14
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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