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Interaction of PABPC1 with the translation initiation complex is critical to the NMD resistance of AUG-proximal nonsense mutations.

2011-10-11Journal article Open access
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dc.contributor.authorPeixeiro, Isabel
dc.contributor.authorInácio, Ângela
dc.contributor.authorBarbosa, Cristina
dc.contributor.authorSilva, Ana Luísa
dc.contributor.authorLiebhaber, Stephen
dc.contributor.authorRomão, Luísa
dc.date.accessioned2011-11-30T17:32:58Z
dc.date.available2011-11-30T17:32:58Z
dc.date.issued2011-10-11
dc.description.abstractNonsense-mediated mRNA decay (NMD) is a surveillance pathway that recognizes and rapidly degrades mRNAs containing premature termination codons (PTC). The strength of the NMD response appears to reflect multiple determinants on a target mRNA. We have previously reported that mRNAs containing PTCs in close proximity to the translation initiation codon (AUG-proximal PTCs) can substantially evade NMD. Here, we explore the mechanistic basis for this NMD resistance. We demonstrate that translation termination at an AUG-proximal PTC lacks the ribosome stalling that is evident in an NMD-sensitive PTC. This difference is associated with demonstrated interactions of the cytoplasmic poly(A)-binding protein 1, PABPC1, with the cap-binding complex subunit, eIF4G and the 40S recruitment factor eIF3 as well as the ribosome release factor, eRF3. These interactions, in combination, underlie critical 30–50 linkage of translation initiation with efficient termination at the AUGproximal PTC and contribute to an NMD-resistant PTC definition at an early phase of translation elongation.por
dc.identifier.citationNucleic Acids Res. 2011 Oct 11. [Epub ahead of print]por
dc.identifier.otherESSN: 1362-4962
dc.identifier.otherdoi:10.1093/nar/gkr820
dc.identifier.urihttp://hdl.handle.net/10400.18/334
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherOxford University Presspor
dc.relation.publisherversionhttp://nar.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=21989405por
dc.subjectMammalian nonsense-mediated mRNA decay (NMD)por
dc.subjectTranslation initiationpor
dc.subjectAUG-proximal nonsense-mutated mRNAspor
dc.subjectPoly(A)-binding protein (PABP)por
dc.subjectPremature termination codon (PTC)por
dc.subjectGenética funcional e estruturalpor
dc.titleInteraction of PABPC1 with the translation initiation complex is critical to the NMD resistance of AUG-proximal nonsense mutations.por
dc.typejournal article
dspace.entity.typePublication
oaire.citation.titleNucleic Acids Researchpor
rcaap.rightsopenAccesspor
rcaap.typearticlepor

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