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Translation of ABCE1 Is Tightly Regulated by Upstream Open Reading Frames in Human Colorectal Cells

2021-07-29Journal article Open access
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dc.contributor.authorSilva, Joana
dc.contributor.authorNina, Pedro
dc.contributor.authorRomão, Luísa
dc.date.accessioned2022-02-07T16:20:44Z
dc.date.available2022-02-07T16:20:44Z
dc.date.issued2021-07-29
dc.descriptionThis article belongs to the Special Issue mRNA Metabolism in Health and Disease.pt_PT
dc.description.abstractATP-binding cassette subfamily E member 1 (ABCE1) belongs to the ABC protein family of transporters; however, it does not behave as a drug transporter. Instead, ABCE1 actively participates in different stages of translation and is also associated with oncogenic functions. Ribosome profiling analysis in colorectal cancer cells has revealed a high ribosome occupancy in the human ABCE1 mRNA 5'-leader sequence, indicating the presence of translatable upstream open reading frames (uORFs). These cis-acting translational regulatory elements usually act as repressors of translation of the main coding sequence. In the present study, we dissect the regulatory function of the five AUG and five non-AUG uORFs identified in the human ABCE1 mRNA 5'-leader sequence. We show that the expression of the main coding sequence is tightly regulated by the ABCE1 AUG uORFs in colorectal cells. Our results are consistent with a model wherein uORF1 is efficiently translated, behaving as a barrier to downstream uORF translation. The few ribosomes that can bypass uORF1 (and/or uORF2) must probably initiate at the inhibitory uORF3 or uORF5 that efficiently repress translation of the main ORF. This inhibitory property is slightly overcome in conditions of endoplasmic reticulum stress. In addition, we observed that these potent translation-inhibitory AUG uORFs function equally in cancer and in non-tumorigenic colorectal cells, which is consistent with a lack of oncogenic function. In conclusion, we establish human ABCE1 as an additional example of uORF-mediated translational regulation and that this tight regulation contributes to control ABCE1 protein levels in different cell environments.pt_PT
dc.description.sponsorshipThis research was partially funded by Fundação para a Ciência e a Tecnologia (UID/MULTI/04046/2013 to BioISI from FCT/MCTES/PIDDAC). Joana Silva was acknowledged with financial support from a fellowship from Fundação para a Ciência e a Tecnologia (SFRH/BD/106081/2015).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationBiomedicines. 2021 Jul 29;9(8):911. doi: 10.3390/biomedicines9080911pt_PT
dc.identifier.doi10.3390/biomedicines9080911pt_PT
dc.identifier.issn2227-9059
dc.identifier.urihttp://hdl.handle.net/10400.18/7940
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationFRH/BD/106081/2015pt_PT
dc.relation.publisherversionhttps://www.mdpi.com/2227-9059/9/8/911pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectColorectal Cancerpt_PT
dc.subjectTranslational Regulationpt_PT
dc.subjectuORFspt_PT
dc.subjectABCE1pt_PT
dc.subjectmRNA Metabolismpt_PT
dc.subjectGenómica Funcionalpt_PT
dc.subjectGenómica Funcional e Estruturalpt_PT
dc.subjectDoenças Genéticaspt_PT
dc.titleTranslation of ABCE1 Is Tightly Regulated by Upstream Open Reading Frames in Human Colorectal Cellspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FMulti%2F04046%2F2013/PT
oaire.citation.issue8pt_PT
oaire.citation.startPage911pt_PT
oaire.citation.titleBiomedicinespt_PT
oaire.citation.volume9pt_PT
oaire.fundingStream5876
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
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.embargofctAcesso de acordo com política editorial da revista.pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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relation.isAuthorOfPublication.latestForDiscoverye2eb8254-24ed-4bfc-b478-3e9022f729e2
relation.isProjectOfPublicationdc84f768-e6f2-4eea-b294-6c8ebbd1a156
relation.isProjectOfPublication.latestForDiscoverydc84f768-e6f2-4eea-b294-6c8ebbd1a156

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