Publication
Regulation of nonsense-mediated mRNA decay (NMD) and the transcriptome: implications for physiology and myocardial infarction
| dc.contributor.author | Fernandes, Rafael | |
| dc.contributor.author | Bourbon, Mafalda | |
| dc.contributor.author | Romão, Luísa | |
| dc.date.accessioned | 2017-03-07T11:35:27Z | |
| dc.date.embargo | 2025 | |
| dc.date.issued | 2016-07-23 | |
| dc.description.abstract | Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that recognizes and selectively degrades mRNAs carrying premature translation termination codons (PTCs) that would otherwise lead to the production of potentially harmful truncated proteins (1). Recent studies demonstrated that NMD also targets physiologic mRNAs transcribed from a large subset of wild-type genes, being responsible for the regulation of up to 10% of the mammalian transcriptome (2,3). This raises the possibility that NMD itself is under regulatory control. Indeed, recent studies have shown that NMD activity is modulated in specific cell types and that key components of the NMD pathway are regulated by several pathways, including NMD itself (4). Cellular stress, such as endoplasmic reticulum (ER) stress, hypoxia, reactive oxygen species, and nutrient deprivation also modulates the magnitude of NMD by mechanisms that are beginning to be understood (5). For example, the activation of kinases, as part of the cell-stress corrective pathways, induces the phosphorylation of the eukaryotic initiation factor 2 alpha (eIF2α), reducing protein translation and thus impairing NMD activity (6,7). There is currently great interest in decoding the mechanisms that couple stress signaling to human pathology. Only recently has ER stress been considered a potential contributor to cardiac and vascular diseases (8). Myocardial infarction is a pathological state that occurs during ischemia, where there is nutrient and oxygen deprivation in the heart, causing aggregation of proteins in the ER. This aggregation triggers ER stress and the three arms of the unfolded protein response (UPR), to mitigate or eliminate the stress (8). Given that NMD can respond to ER stress (6), here we aim to study 1) how NMD is regulated in cardiomyocytes under stress conditions, and 2) what is the influence of NMD on the transcriptome of cardiomyocytes and how it is involved in the cell-stress corrective strategies. So far, we have built a database that contains around 149 transcripts which are natural NMD-targets and are dysregulated under stress conditions, based on data from transcriptomic and UPF1-silencing studies. Using bioinformatics and gene ontology analysis we have classified the transcripts by biological function, and we intend to choose a few molecular targets for further studies in cardiomyocytes cultured cells in order to accomplish the objectives proposed. | pt_PT |
| dc.description.version | N/A | pt_PT |
| dc.identifier.uri | http://hdl.handle.net/10400.18/4522 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | no | pt_PT |
| dc.publisher | Instituto Nacional de Saúde Doutor Ricardo Jorge, IP | pt_PT |
| dc.subject | Genómica Funcional e Estrutural | pt_PT |
| dc.subject | Expressão Génica | pt_PT |
| dc.subject | Myocardial Infarction | pt_PT |
| dc.title | Regulation of nonsense-mediated mRNA decay (NMD) and the transcriptome: implications for physiology and myocardial infarction | pt_PT |
| dc.type | conference object | |
| dspace.entity.type | Publication | |
| oaire.citation.conferencePlace | Santa Cruz, Torres Vedras | pt_PT |
| oaire.citation.title | 1st BioSys/BioISI Summer Retreat, 23-24 julho 2016 | pt_PT |
| rcaap.rights | embargoedAccess | pt_PT |
| rcaap.type | conferenceObject | pt_PT |