Publication
The mechanism through which nonsense mutations are recognized as premature translation-termination codons
| dc.contributor.author | Onofre, Claudia | |
| dc.contributor.author | Menezes, Juliane | |
| dc.contributor.author | Peixeiro, Isabel | |
| dc.contributor.author | Barbosa, Cristina | |
| dc.contributor.author | Romão, Luísa | |
| dc.date.accessioned | 2018-03-02T16:15:55Z | |
| dc.date.embargo | 2025-12-31 | |
| dc.date.issued | 2017-05-27 | |
| dc.description.abstract | About one third of the gene mutations found in human genetic disorders, including cancer, result in premature termination codons (PTCs) and the rapid degradation of their mRNAs by nonsense-mediated decay (NMD). NMD controls the quality of eukaryotic gene expression. The strength of the NMD response appears to reflect multiple determinants on a target mRNA. 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 provide 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 mRNA translation initiation. | pt_PT |
| dc.description.sponsorship | FCT/PTDC/BIMONC/4890/2014 | pt_PT |
| dc.description.version | N/A | pt_PT |
| dc.identifier.uri | http://hdl.handle.net/10400.18/5134 | |
| dc.language.iso | eng | pt_PT |
| dc.subject | Premature Termination Codons (PTCs) | pt_PT |
| dc.subject | Nonsense-mediated Decay (NMD) | pt_PT |
| dc.subject | Expressão Génica | pt_PT |
| dc.subject | Genómica Funcional e Estrutural | pt_PT |
| dc.title | The mechanism through which nonsense mutations are recognized as premature translation-termination codons | pt_PT |
| dc.type | conference object | |
| dspace.entity.type | Publication | |
| oaire.citation.conferencePlace | Copenhagen, Denmark | pt_PT |
| oaire.citation.title | European Society of Human Genetics (ESHG) Conferences, 27-30 may 2017 | pt_PT |
| rcaap.embargofct | Os resultados ainda não foram publicados | pt_PT |
| rcaap.rights | embargoedAccess | pt_PT |
| rcaap.type | conferenceObject | pt_PT |