Publication
The human mTOR transcript allows cap-independent translation that insures its expression and function during inhibition of global translation
| dc.contributor.author | Marques-Ramos, Ana | |
| dc.contributor.author | Menezes, Juliane | |
| dc.contributor.author | Candeias, Marco | |
| dc.contributor.author | Willcocks, Mariam | |
| dc.contributor.author | Lacerda, Rafaela | |
| dc.contributor.author | Teixeira, Alexandre | |
| dc.contributor.author | Locker, Nicola | |
| dc.contributor.author | Romão, Luísa | |
| dc.date.accessioned | 2017-03-03T19:00:23Z | |
| dc.date.embargo | 2025 | |
| dc.date.issued | 2016-10-05 | |
| dc.description.abstract | The mammalian target of rapamycin (mTOR) is a conserved serine/threonine kinase that integrates signals from the cellular nutrient- and energy-status, acting namely on the protein synthesis machinery. Deregulation of mTOR signaling is implicated in major diseases, such as cancer, mainly due to its role in regulating protein synthesis. Major advances are emerging regarding the regulators and effects of mTOR signaling pathway; however, regulation of mTOR gene expression is not well known. Here, we show that the 5’ untranslated region of the human mTOR transcript forms a highly folded RNA scaffold capable of binding directly to the 40S ribosomal subunit. We further demonstrate that this cis-acting RNA regulon is active both in normal and stress conditions, and that its activation status in response to translational adverse conditions parallels mTOR protein levels. Moreover, our data reveal that the cap-independent translation of mTOR is necessary for its ability to induce cell cycle progression into S-phase. These results suggest a novel regulatory mechanism of mTOR gene expression that integrates the protein profile rearrangement triggered by global translation inhibitory conditions. | pt_PT |
| dc.description.sponsorship | This work was partially supported by Fundação Merck Sharp and Dohme and Fundação para a Ciência e a Tecnologia (FCT) through center grant UID/MULTI/04046/2013 (to BioISI) and research grant PTDC/BIM-ONC/4890/2014. Ana Marques-Ramos, Juliane Menezes, and Rafaela Lacerda were supported by Fellowships from FCT [SFRH/BD/33462/2008 to A.M.-R., FCT/SFRH/BPD/98360/2013 to J.M., and SFRH/BD/74778/2010 to R.L.]. Marco Marques Candeias was supported by fellowships from the Japan Society for the Promotion of Science (JSPS/FF1/184) and AXA Research Fund and JSPS Grant-in-Aid for Young Scientists (B) (16K21111). | pt_PT |
| dc.description.version | N/A | pt_PT |
| dc.identifier.uri | http://hdl.handle.net/10400.18/4477 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc/4.0/ | pt_PT |
| dc.subject | Genómica Funcional e Estrutural | pt_PT |
| dc.subject | Expressão Génica | pt_PT |
| dc.subject | mTOR | pt_PT |
| dc.subject | Mammalian Target of Rapamycin | pt_PT |
| dc.title | The human mTOR transcript allows cap-independent translation that insures its expression and function during inhibition of global translation | pt_PT |
| dc.type | conference object | |
| dspace.entity.type | Publication | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/5876/UID%2FMulti%2F04046%2F2013/PT | |
| oaire.citation.conferencePlace | Heidelberg, Alemanha | pt_PT |
| oaire.citation.title | EMBO | EMBL Symposium: The Complex Life of mRNA, 5-8 October 2016 | pt_PT |
| oaire.fundingStream | 5876 | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| rcaap.rights | embargoedAccess | pt_PT |
| rcaap.type | conferenceObject | pt_PT |
| relation.isProjectOfPublication | dc84f768-e6f2-4eea-b294-6c8ebbd1a156 | |
| relation.isProjectOfPublication.latestForDiscovery | dc84f768-e6f2-4eea-b294-6c8ebbd1a156 |