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Unraveling the role of internal ribosome entry site (IRES) mediated translation in human UPF1 expression and function

2021-09-07Conference object Restricted access
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dc.contributor.authorLacerda, Rafaela
dc.contributor.authorMenezes, Juliane
dc.contributor.authorRomão, Luísa
dc.date.accessioned2022-07-09T15:54:15Z
dc.date.available2022-12-31T01:30:32Z
dc.date.issued2021-09-07
dc.description.abstractUp-frameshift 1 (UPF1) is the key factor in nonsense-mediated mRNA decay (NMD, a mechanism that degrades transcripts carrying premature translation termination codons. Besides its role in NMD, UPF1 has also a role in other mechanisms, such as cell cycle progression, being crucial for the G1/S transition, and in telomere maintenance and homeostasis. Furthermore, it has also been identified as having tumour suppressor activity in different cancers, such as hepatocellular carcinoma. Our data supports the existence of an IRES within the human UPF1 5’ untranslated region (UTR). In fact, using a bicistronic reporter system, we observed that UPF1 5’UTR can mediate internal translation in a 5’ cap-independent manner, both in normal and under stress conditions. We concluded that the first 100 nucleotides and the last 125 (out of a total of 275) are the minimal sequences essential for the identified IRES activity. According to the in silico predicted secondary structure, these two segments correspond to two stem-loops. Now, we are experimentally confirming this predicted secondary structure, and understanding the physiological role of this IRES-mediated activity in the NMD process. Also, we are testing its importance for UPF1 function as a tumour suppressor. For that, we are using custom-made antisense oligonucleotides that specifically target those stem-loops and see to what extent they inhibit UPF1 IRES-mediated activity and how such inhibition will play a role in the cell and the functions in which UPF1 participates. Also, we are testing some hallmarks of cancer, such as proliferation, invasion, and apoptosis inhibition when the UPF1 IRES is impaired. With this work, we wish to unravel a new layer of knowledge in gene expression regulation of UPF1.pt_PT
dc.description.sponsorshipFCTpt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.urihttp://hdl.handle.net/10400.18/8142
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.subjectNonsense-mediated mRNA Decaypt_PT
dc.subjectUPF1pt_PT
dc.subjectUp-frameshift 1pt_PT
dc.subjectGenómica Funcionalpt_PT
dc.subjectGenómica Funcional e Estruturalpt_PT
dc.subjectDoenças Genéticaspt_PT
dc.titleUnraveling the role of internal ribosome entry site (IRES) mediated translation in human UPF1 expression and functionpt_PT
dc.typeconference object
dspace.entity.typePublication
oaire.citation.conferencePlace(Online)pt_PT
oaire.citation.titleProtein Synthesis and Translational Control-EMBL Conference, 7-10 Sep 2021pt_PT
person.familyNameRomão
person.givenNameLuísa
person.identifierhttps://scholar.google.pt/citations?hl=pt-PT&user=CAHjIsoAAAAJ&cstart=60&pagesize=20
person.identifier.ciencia-idEB19-DF07-EB37
person.identifier.orcid0000-0002-5061-5287
person.identifier.scopus-author-idhttp://www.scopus.com/authid/detail.url?authorId=6602834878
rcaap.rightsopenAccesspt_PT
rcaap.typeconferenceObjectpt_PT
relation.isAuthorOfPublicatione2eb8254-24ed-4bfc-b478-3e9022f729e2
relation.isAuthorOfPublication.latestForDiscoverye2eb8254-24ed-4bfc-b478-3e9022f729e2

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