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

TitleInteraction of PABPC1 with the translation initiation complex is critical to the NMD resistance of AUG-proximal nonsense mutations.
Publication TypeJournal Article
Year of Publication2012
AuthorsPeixeiro, I, Inácio, Â, Barbosa, C, Silva, ALuísa, Liebhaber, SA, Romão, L
JournalNucleic Acids Res
Volume40
Issue3
Pagination1160-73
Date Published2012 Feb
ISSN1362-4962
KeywordsCodon, Initiator, Codon, Nonsense, Codon, Terminator, Eukaryotic Initiation Factor-3, Eukaryotic Initiation Factor-4G, Eukaryotic Initiation Factors, HeLa Cells, Humans, Nonsense Mediated mRNA Decay, Peptide Chain Initiation, Translational, Peptide Chain Termination, Translational, Peptide Termination Factors, Poly(A)-Binding Protein I, Ribosomes, RNA, Messenger, RNA-Binding Proteins
Abstract

Nonsense-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 3'-5' linkage of translation initiation with efficient termination at the AUG-proximal PTC and contribute to an NMD-resistant PTC definition at an early phase of translation elongation.

DOI10.1093/nar/gkr820
Alternate JournalNucleic Acids Res.
Citation Key10.1093/nar/gkr820
PubMed ID21989405
PubMed Central IDPMC3273812