Publication
Human UPF1 translation initiation is regulated by a cap-independent mechanism
| dc.contributor.author | Lacerda, Rafaela | |
| dc.contributor.author | Menezes, Juliane | |
| dc.contributor.author | Marques-Ramos, Ana | |
| dc.contributor.author | Teixeira, Alexandre | |
| dc.contributor.author | Romão, Luísa | |
| dc.date.accessioned | 2016-03-04T16:45:56Z | |
| dc.date.available | 2020-12-31T01:30:11Z | |
| dc.date.issued | 2015-11-06 | |
| dc.description.abstract | Gene expression is a very intricate process comprising several tightly regulated steps. One of those is translation initiation that, under normal circumstances, is mostly cap-dependent. However, some proteins can initiate translation via a cap-independent mechanism. This allows the maintenance of protein synthesis under conditions that reduce global protein synthesis. Human up-frameshift 1 (UPF1) has a key role in several cellular processes such as nonsense-mediated mRNA decay, telomere replication and homeostasis, and cell cycle progression, suggesting a tight regulation in order to prevent abnormal proliferation. These data suggest UPF1 might initiate translation in a cap-independent way, allowing the cell to overcome stress conditions that impair cap-dependent translation. To test this hypothesis, we cloned the UPF1 5’UTR in a dicistronic vector and transfected cervical and colorectal cancer cell lines with either this construct or the control counterparts. We observed a 15- to 25-fold increase in relative luciferase activity of the UPF1 5’UTR-containing construct compared to the levels obtained from the empty counterpart in all tested cell lines, suggesting a cap-independent translation initiation. Cells transfection with in vitro transcribed mRNAs resulted in a 2-fold increase in protein levels, confirming translation can occur in a cap-independent way. This is maintained under conditions of global protein synthesis inhibition. Deletional analysis of the UPF1 5’UTR revealed that the minimal core required for cap-independent activity is present either within the first 100 nucleotides or within the last 125. Further experiments are being undertaken to understand the biological role of a cap-independent mechanism for the translation of UPF1 and how it contributes to the roles UPF1 plays in the cell. | pt_PT |
| dc.description.sponsorship | FCT, BioISI, MSD | pt_PT |
| dc.identifier.uri | http://hdl.handle.net/10400.18/3658 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.subject | Genómica Funcional e Estrutural | pt_PT |
| dc.subject | Expressão Génica | pt_PT |
| dc.subject | Síntese Proteica | pt_PT |
| dc.title | Human UPF1 translation initiation is regulated by a cap-independent mechanism | pt_PT |
| dc.type | conference object | |
| dspace.entity.type | Publication | |
| oaire.citation.conferencePlace | Porto, Portugal | pt_PT |
| oaire.citation.title | 19ª Reunião Anual da Sociedade Portuguesa de Genética Humana, 5-7 novembro 2015 | pt_PT |
| rcaap.rights | openAccess | pt_PT |
| rcaap.type | conferenceObject | pt_PT |