Publication
Nonsense-mediated decay resistance of AUG-proximal nonsense-mutated transcripts relies on the interaction of PABPC1 with the translation initiation complex
| dc.contributor.author | Peixeiro, Isabel | |
| dc.contributor.author | Barbosa, Cristina | |
| dc.contributor.author | Romão, Luísa | |
| dc.date.accessioned | 2012-10-24T15:58:55Z | |
| dc.date.available | 2012-10-24T15:58:55Z | |
| dc.date.issued | 2012-09-01 | |
| dc.description | Apresentação oral por convite. | por |
| dc.description.abstract | Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that recognizes and rapidly degrades mRNAs containing a premature termination codon (PTC). The unified model for NMD proposes that the decision of NMD triggering is the outcome of the competition between the cytoplasmatic poly(A)-binding protein 1 (PABPC1) and the NMD effector UPF1 for the termination complex. Consequently, PTCs located far, in a linear sense, from the poly(A) tail and associated PABPC1, in mRNAs containing downstream exon junction complexes (EJCs), are expected to elicit NMD. Nevertheless, we have reported that human b-globin mRNAs containing PTCs in close proximity to the translation initiation codon (AUG-proximal PTCs) can substantially evade NMD. We have reported that translation termination at an AUG-proximal PTC lacks the ribosome stalling that is evident in an NMD-sensitive PTC. In fact, we have shown that the establishment of an efficient translation termination reaction at the AUG-proximal PTC is dependent on PABPC1 interaction with the initiation factor eIF4G and with the release factor eRF3 at the terminating ribosome. These interactions 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. Furthermore, we provide strong evidence that the eIF3 is involved in delivering eIF4G-associated PABPC1 into the vicinity of the AUG-proximal PTC. This work corroborates a role for PABPC1 on NMD evasion of transcripts carrying an AUG-proximal PTC and provides further insights into the mechanistic details of PTC definition and translation initiation. | por |
| dc.identifier.uri | http://hdl.handle.net/10400.18/1042 | |
| dc.language.iso | eng | por |
| dc.peerreviewed | yes | por |
| dc.publisher | Instituto Nacional de Saúde Doutor Ricardo Jorge, IP | por |
| dc.subject | Genómica Funcional e Estrutural | por |
| dc.title | Nonsense-mediated decay resistance of AUG-proximal nonsense-mutated transcripts relies on the interaction of PABPC1 with the translation initiation complex | por |
| dc.type | conference object | |
| dspace.entity.type | Publication | |
| oaire.citation.conferencePlace | Tavira, Portugal | por |
| oaire.citation.title | FEBS International Workshop on “New Developments in RNA Biology", Sept 1- 4 2012 | por |
| rcaap.rights | openAccess | por |
| rcaap.type | conferenceObject | por |