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Resistance of mRNAs with AUG-proximal nonsense mutations to nonsense-mediated decay reflects variables of mRNA structure and translational activity.

dc.contributor.authorPereira, Francisco
dc.contributor.authorKong, Jian
dc.contributor.authorSiva, Ana Luísa
dc.contributor.authorLiebhaber, Stephen A
dc.contributor.authorRomão, Luísa
dc.date.accessioned2016-02-16T17:10:07Z
dc.date.available2016-02-16T17:10:07Z
dc.date.issued2015-07-27
dc.descriptionAcessível em: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4513866/pt_PT
dc.description.abstractNonsense-mediated mRNA decay (NMD) is a surveillance pathway that recognizes and selectively degrades mRNAs carrying premature termination codons (PTCs). The level of sensitivity of a PTC-containing mRNA to NMD is multifactorial. We have previously shown that human β-globin mRNAs carrying PTCs in close proximity to the translation initiation AUG codon escape NMD. This was called the 'AUG-proximity effect'. The present analysis of nonsense codons in the human α-globin mRNA illustrates that the determinants of the AUG-proximity effect are in fact quite complex, reflecting the ability of the ribosome to re-initiate translation 3' to the PTC and the specific sequence and secondary structure of the translated ORF. These data support a model in which the time taken to translate the short ORF, impacted by distance, sequence, and structure, not only modulates translation re-initiation, but also impacts on the exact boundary of AUG-proximity protection from NMD.pt_PT
dc.identifier.citationNucleic Acids Res. 2015 Jul 27;43(13):6528-44. doi: 10.1093/nar/gkv588. Epub 2015 Jun 11.pt_PT
dc.identifier.doi10.1093/nar/gkv588pt_PT
dc.identifier.issn0305-1048
dc.identifier.urihttp://hdl.handle.net/10400.18/3346
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherOxford University Presspt_PT
dc.relation.publisherversionhttp://nar.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=26068473pt_PT
dc.subjectExpressão Génicapt_PT
dc.subjectGenómica Funcional e Estruturalpt_PT
dc.titleResistance of mRNAs with AUG-proximal nonsense mutations to nonsense-mediated decay reflects variables of mRNA structure and translational activity.pt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage6544pt_PT
oaire.citation.startPage6528pt_PT
oaire.citation.titleNucleic Acids Researchpt_PT
oaire.citation.volume43(13)pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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