Publication
How mRNA translation can modulate nonsense-mediated decay
| dc.contributor.author | Romão, Luísa | |
| dc.date.accessioned | 2018-03-21T17:19:22Z | |
| dc.date.embargo | 2025-12-31 | |
| dc.date.issued | 2017-03-08 | |
| dc.description.abstract | About one third of the gene mutations found in human genetic disorders, including cancer, result in premature translation-termination codons (PTCs) and the rapid degradation of the corresponding mRNAs by nonsense-mediated decay (NMD). However, we have found that human mRNAs with a PTC in close proximity to the translation initiation codon (AUG-proximal PTC) can substantially escape NMD, which contradicts the current models for this mechanism. In fact, 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 eukaryotic release factor 3 (eRF3) with a consequent enhancement of the termination reaction and repression of the NMD response. Here, I will provide strong evidence that the eukaryotic initiation factor 3 (eIF3) is involved in delivering eIF4G-associated PABPC1 into the vicinity of the AUG-proximal PTC, and I will dissect the biochemical interactions of the eIF3 subunits in bridging PABPC1/eIF4G complex to the 40S ribosomal subunit. | 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/10400.18/5423 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | no | pt_PT |
| dc.subject | Gene Mutations | 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 | How mRNA translation can modulate nonsense-mediated decay | pt_PT |
| dc.type | lecture | |
| dspace.entity.type | Publication | |
| oaire.citation.conferencePlace | Lisboa, Portugal | pt_PT |
| oaire.citation.title | Seminário no âmbito de BioSys PhD programme at BioISI, Faculdade de Ciências da Universidade de Lisboa, 8 março 2017 | pt_PT |
| rcaap.embargofct | Os resultados ainda não foram publicados. | pt_PT |
| rcaap.rights | embargoedAccess | pt_PT |
| rcaap.type | lecture | pt_PT |