Publicação
The potential function of alternative translation initiation of Argonaute 1 in cancer
| datacite.subject.fos | Ciências Médicas | |
| datacite.subject.sdg | 03:Saúde de Qualidade | |
| dc.contributor.author | Vieira da Silva, Verónica | |
| dc.contributor.author | Lacerda, Rafaela | |
| dc.contributor.author | Romão, Luísa | |
| dc.date.accessioned | 2026-02-09T13:51:19Z | |
| dc.date.available | 2026-02-09T13:51:19Z | |
| dc.date.issued | 2025-06-05 | |
| dc.description.abstract | Translation is one of the most regulated and energy-consuming cellular processes crucial for proper cell function. Translation is initiated by the canonical cap-dependent mechanism. However, under stress conditions, the initiation of canonical translation is inhibited, which allows the translation of specific proteins via alternative mechanisms. This project aims to understand the biological relevance of alternative protein synthesis mechanisms in Argonaute 1 (AGO1) expression. The AGO1 protein is involved in microRNA regulation, gene expression modulation and inhibition. AGO1 is also involved in the regulation of gene expression by RNA interference (RNAi), and its deregulation can lead to the activation of oncogenes or the suppression of tumor suppressor genes, contributing to the development and progression of cancer. Our work has shown that AGO1 mRNA can be translated through a cap-independent initiation mechanism. An upstream open reading frame (uORF) has also been identified in its 5’ untranslated region (5’UTR), which may play a role in the initiation of AGO1 translation. The results showed that the 5’UTR of human AGO1 supports a cap-independent mechanism of translation initiation, which is maintained under stress conditions. However, our analyses did not provide conclusive evidence for a regulatory role of the uORF in this initiation process. To this end, the 5’UTR of human AGO1 was cloned into a bicistronic vector containing Renilla (RLuc) and Firefly luciferase (FLuc), with FLuc positioned downstream of the 5’UTR. Luminometry assays will be used to evaluate the relative FLuc/RLuc translation efficiency under the control of the AGO1 5’UTR. The same approach will be used with monocistronistic reporter vectors, contaning only FLuc. This project aims to understand how these alternative mechanisms of mRNA translation initiation can influence AGO1 expression and help explain their potential roles in certain pathologies and cancer progression, such as colorectal cancer. | eng |
| dc.description.sponsorship | This work was partially supported by Instituto Nacional de Saúde Doutor Ricardo Jorge and Fundação para a Ciência e a Tecnologia [UIDB/04046/2020 (https://doi.org/10.54499/UIDB/04046/2020) and UIDP/04046/2020 (https://doi.org/10.54499/UIDP/04046/2020). R.L. was supported by Grant SFRH/BD/74778/2010 from FCT. | |
| dc.identifier.uri | http://hdl.handle.net/10400.18/10854 | |
| dc.language.iso | eng | |
| dc.peerreviewed | yes | |
| dc.relation | Biosystems and Integrative Sciences Institute | |
| dc.relation | Biosystems and Integrative Sciences Institute | |
| dc.relation | NON-CANONICAL INTERNAL RIBOSOME ENTRY SITE-MEDIATED TRANSLATION: IDENTIFICATION OF NEW PROTEINS INVOLVED IN COLORECTAL CANCER | |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| dc.subject | Cancer | |
| dc.subject | Argonaute 1 | |
| dc.subject | Stress | |
| dc.subject | Translation | |
| dc.subject | Genómica Funcional e Estrutural | |
| dc.title | The potential function of alternative translation initiation of Argonaute 1 in cancer | eng |
| dc.type | conference object | |
| dspace.entity.type | Publication | |
| oaire.awardTitle | Biosystems and Integrative Sciences Institute | |
| oaire.awardTitle | Biosystems and Integrative Sciences Institute | |
| oaire.awardTitle | NON-CANONICAL INTERNAL RIBOSOME ENTRY SITE-MEDIATED TRANSLATION: IDENTIFICATION OF NEW PROTEINS INVOLVED IN COLORECTAL CANCER | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04046%2F2020/PT | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04046%2F2020/PT | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F74778%2F2010/PT | |
| oaire.citation.conferenceDate | 2025-06-05 | |
| oaire.citation.conferencePlace | Oeiras, Portugal | |
| oaire.citation.title | VI International Conference of the Portuguese Society of Genetics, 5-6 June 2025 | |
| oaire.fundingStream | 6817 - DCRRNI ID | |
| oaire.fundingStream | 6817 - DCRRNI ID | |
| oaire.version | http://purl.org/coar/version/c_b1a7d7d4d402bcce | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| relation.isProjectOfPublication | dc433369-36fd-4935-bd52-c56aa49c72e1 | |
| relation.isProjectOfPublication | e8390b4d-1833-4925-a0ab-5fff0527efaa | |
| relation.isProjectOfPublication | f858aa0b-b6ed-4842-b58a-1d78c3c1dba8 | |
| relation.isProjectOfPublication.latestForDiscovery | dc433369-36fd-4935-bd52-c56aa49c72e1 |
