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The interplay between mRNA translation and nonsense-mediated decay in transcripts with short open reading frames

2016-09-13Lecture Restricted access
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dc.contributor.authorOnofre, Cláudia
dc.contributor.authorMenezes, Juliane
dc.contributor.authorPeixeiro, Isabel
dc.contributor.authorBarbosa, Cristina
dc.contributor.authorRomão, Luísa
dc.date.accessioned2017-03-06T16:06:23Z
dc.date.embargo2025
dc.date.issued2016-09-13
dc.description.abstractMammalian nonsense-mediated mRNA decay (NMD) is a splicing- and translation-dependent surveillance pathway that recognizes and selectively degrades mRNAs carrying premature termination codons (PTCs). In addition, several studies have also implicated NMD in the regulation of steady-state levels of physiological mRNAs, and examples of natural NMD targets are transcripts containing upstream short open reading frames or long 3’ untranslated regions. The strength of the NMD response appears to reflect multiple determinants on a target mRNA. In general, the location of a PTC greater than 50 nucleotides upstream to the last exon-exon junction constitutes a major determinant of NMD. However, we have reported that human mRNAs with a PTC in close proximity to the translation initiation codon (AUG-proximal PTC), and thus, with a short open reading frame, can substantially escape NMD. Our data support a model in which cytoplasmic poly(A)-binding protein 1 (PABPC1) is brought into close proximity with an AUG-proximal PTC via interactions with the translation initiation complexes. This proximity of PABPC1 to the AUG-proximal PTC allows PABPC1 to interact with eRF3 with a consequent enhancement of the release reaction and repression of the NMD response. Here, we present strong evidence that the eIF3 is involved in delivering eIF4G-associated PABPC1 into the vicinity of the AUG-proximal PTC. In addition, we dissect the biochemical interactions of the eIF3 subunits in bridging PABPC1/eIF4G complex to the 40S ribosomal subunit. Together, our data provide a framework for understanding the mechanistic details of PTC definition and translation initiation.pt_PT
dc.description.sponsorshipThis work was partially supported by Fundação Luso-Americana para o Desenvolvimento and Fundação para a Ciência e a Tecnologia (UID/MULTI/04046/2013 to BioISI from FCT/MCTES/PIDDAC).pt_PT
dc.description.versionN/Apt_PT
dc.identifier.urihttp://hdl.handle.net/10400.18/4508
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.subjectGenómica Funcional e Estruturalpt_PT
dc.subjectExpressão Génicapt_PT
dc.subjectNonsense-mediated mRNA Decaypt_PT
dc.titleThe interplay between mRNA translation and nonsense-mediated decay in transcripts with short open reading framespt_PT
dc.typelecture
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FMulti%2F04046%2F2013/PT
oaire.citation.conferencePlaceCaparica, Lisboa, Portugalpt_PT
oaire.citation.title1st International Caparica Conference in Splicing, 12-14 September 2016pt_PT
oaire.fundingStream5876
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsembargoedAccesspt_PT
rcaap.typelecturept_PT
relation.isProjectOfPublicationdc84f768-e6f2-4eea-b294-6c8ebbd1a156
relation.isProjectOfPublication.latestForDiscoverydc84f768-e6f2-4eea-b294-6c8ebbd1a156

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