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Internal ribosome entry site (IRES)-mediated translation as a putative candidate mechanism to mRNA-based therapies

2021-11-18Conference object Restricted access
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dc.contributor.authorNeto, Maria Inês
dc.contributor.authorLacerda, Rafaela
dc.contributor.authorRomão, Luísa
dc.date.accessioned2022-07-09T15:04:07Z
dc.date.embargo2027-12-31
dc.date.issued2021-11-18
dc.description.abstractUntranslated regions in the messenger RNA (mRNA) are susceptible to the interaction of regulatory elements including proteins or non-coding RNA molecules, being an important hotspot to the study of gene expression regulation. Internal Ribosome Entry Sites (IRES) are secondary structures usually located on the 5’UTR of an mRNA molecule that can recruit the ribosome during initiation of protein synthesis without the involvement of the cap structure. This mechanism tends to appear when the cell is under stress conditions, which might include the presence of oncogenes, growth factors or proteins involved in programmed cell death. This work focuses on the human AGO1, an important key player for RNA-mediated gene silencing, and whether its 5’UTR is capable of driving cap-independent translation initiation. To achieve this goal, a construct containing the 5’UTR of human AGO1 was cloned, taking advantage of a bicistronic vector containing two reporter genes, Renilla luciferase (RLuc) and firefly luciferase (FLuc), the last one cloned downstream from the 5’UTR. We performed luminometry assays to assess the relative translation efficiency of FLuc, which is under the control of AGO1 5’UTR. The results showed that human AGO1 5’UTR mediates a cap-independent eIF4G-dependent mechanism of translation initiation enhanced by a free 5’ end. Also, we saw that this alternative mechanism is maintained, and even enhanced, under stress conditions, such as the knock-down of eukaryotic initiation factor 4E, the protein that directly binds to the cap structure. We are currently investigating what is the minimal sequence required for IRES-mediated translation. Combining these results with emerging RNA-based therapies will be helpful to develop novel strategies to prevent and treat disorders, such as cancer, involving dysregulation of AGO1 translation.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.urihttp://hdl.handle.net/10400.18/8129
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.subjectUntranslated Regions in the Messenger RNApt_PT
dc.subjectmRNApt_PT
dc.subjectRNA Cancerpt_PT
dc.subjectGenómica Funcionalpt_PT
dc.subjectGenómica Funcional e Estruturalpt_PT
dc.subjectDoenças Genéticaspt_PT
dc.titleInternal ribosome entry site (IRES)-mediated translation as a putative candidate mechanism to mRNA-based therapiespt_PT
dc.typeconference object
dspace.entity.typePublication
oaire.citation.conferencePlace(Online)pt_PT
oaire.citation.title25th Annual Meeting of the Portuguese Society of Human Genetics, 18-19 Novembro 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.rightsembargoedAccesspt_PT
rcaap.typeconferenceObjectpt_PT
relation.isAuthorOfPublicatione2eb8254-24ed-4bfc-b478-3e9022f729e2
relation.isAuthorOfPublication.latestForDiscoverye2eb8254-24ed-4bfc-b478-3e9022f729e2

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