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The potential function of alternative translation initiation of Argonaute 1 in cancer

datacite.subject.fosCiências Médicas
datacite.subject.sdg03:Saúde de Qualidade
dc.contributor.authorVieira da Silva, Verónica
dc.contributor.authorLacerda, Rafaela
dc.contributor.authorRomão, Luísa
dc.date.accessioned2026-02-09T13:51:19Z
dc.date.available2026-02-09T13:51:19Z
dc.date.issued2025-06-05
dc.description.abstractTranslation 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.sponsorshipThis 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.urihttp://hdl.handle.net/10400.18/10854
dc.language.isoeng
dc.peerreviewedyes
dc.relationBiosystems and Integrative Sciences Institute
dc.relationBiosystems and Integrative Sciences Institute
dc.relationNON-CANONICAL INTERNAL RIBOSOME ENTRY SITE-MEDIATED TRANSLATION: IDENTIFICATION OF NEW PROTEINS INVOLVED IN COLORECTAL CANCER
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectCancer
dc.subjectArgonaute 1
dc.subjectStress
dc.subjectTranslation
dc.subjectGenómica Funcional e Estrutural
dc.titleThe potential function of alternative translation initiation of Argonaute 1 in cancereng
dc.typeconference object
dspace.entity.typePublication
oaire.awardTitleBiosystems and Integrative Sciences Institute
oaire.awardTitleBiosystems and Integrative Sciences Institute
oaire.awardTitleNON-CANONICAL INTERNAL RIBOSOME ENTRY SITE-MEDIATED TRANSLATION: IDENTIFICATION OF NEW PROTEINS INVOLVED IN COLORECTAL CANCER
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04046%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04046%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F74778%2F2010/PT
oaire.citation.conferenceDate2025-06-05
oaire.citation.conferencePlaceOeiras, Portugal
oaire.citation.titleVI International Conference of the Portuguese Society of Genetics, 5-6 June 2025
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.versionhttp://purl.org/coar/version/c_b1a7d7d4d402bcce
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
relation.isProjectOfPublicationdc433369-36fd-4935-bd52-c56aa49c72e1
relation.isProjectOfPublicatione8390b4d-1833-4925-a0ab-5fff0527efaa
relation.isProjectOfPublicationf858aa0b-b6ed-4842-b58a-1d78c3c1dba8
relation.isProjectOfPublication.latestForDiscoverydc433369-36fd-4935-bd52-c56aa49c72e1

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