Publication
Cap-independent translation ensures mTOR expression and function upon protein synthesis inhibition
| dc.contributor.author | Marques-Ramos, Ana | |
| dc.contributor.author | Romão, Luísa | |
| dc.contributor.author | Candeias, Marco | |
| dc.contributor.author | Menezes, Juliane | |
| dc.contributor.author | Lacerda, Rafaela | |
| dc.contributor.author | Willcocks, M. | |
| dc.contributor.author | Teixeira, Alexandre | |
| dc.contributor.author | Locker, Nicolas | |
| dc.date.accessioned | 2018-01-03T15:45:39Z | |
| dc.date.available | 2018-08-19T00:30:12Z | |
| dc.date.issued | 2017-11 | |
| dc.description.abstract | The mechanistic/mammalian target of rapamycin (mTOR) is a conserved serine/threonine kinase that integrates cellular signals from the nutrient and energy status to act, namely, on the protein synthesis machinery. While major advances have emerged regarding the regulators and effects of the mTOR signaling pathway, little is known about the regulation of mTOR gene expression. Here, we show that the human mTOR transcript can be translated in a cap-independent manner, and that its 5' untranslated region (UTR) is a highly folded RNA scaffold capable of binding directly to the 40S ribosomal subunit. We further demonstrate that mTOR is able to bypass the cap requirement for translation both in normal and hypoxic conditions. 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 for mTOR gene expression that integrates the global protein synthesis changes induced by translational 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. A.M.-R., J.M., and R.L. 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 and PTDC/BIM-ONC/4890/2014 to R.L.). M.M.C. was supported by fellowships from the Japan Society for the Promotion of Science (JSPS/FF1/184), AXA Research Fund, JSPS Grant-in-Aid for Young Scientists (B) (16K21111), and PTDC/BIM-ONC/4890/ 2014. | pt_PT |
| dc.description.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.citation | RNA. 2017 Nov;23(11):1712-1728. doi: 10.1261/rna.063040.117. Epub 2017 Aug 18. | pt_PT |
| dc.identifier.doi | 10.1261/rna.063040.117. | pt_PT |
| dc.identifier.issn | 1355-838 | |
| dc.identifier.uri | http://hdl.handle.net/10400.18/4859 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.publisher | RNA Society | pt_PT |
| dc.relation.publisherversion | http://rnajournal.cshlp.org/content/23/11/1712.abstract | pt_PT |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc/4.0/ | pt_PT |
| dc.subject | CITE | pt_PT |
| dc.subject | IRES | pt_PT |
| dc.subject | Cap-Independent Translation | pt_PT |
| dc.subject | Mechanistic Target of Rapamycin (mTOR) | pt_PT |
| dc.subject | Translation Initiation | pt_PT |
| dc.subject | Translational Control | pt_PT |
| dc.subject | Expressão Génica | pt_PT |
| dc.subject | Genómica Funcional e Estrutural | pt_PT |
| dc.title | Cap-independent translation ensures mTOR expression and function upon protein synthesis inhibition | pt_PT |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/5876/UID%2FMulti%2F04046%2F2013/PT | |
| oaire.citation.conferencePlace | USA | pt_PT |
| oaire.citation.endPage | 1728 | pt_PT |
| oaire.citation.issue | 11 | pt_PT |
| oaire.citation.startPage | 1712 | pt_PT |
| oaire.citation.title | RNA | pt_PT |
| oaire.citation.volume | 23 | 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 | article | pt_PT |
| relation.isProjectOfPublication | dc84f768-e6f2-4eea-b294-6c8ebbd1a156 | |
| relation.isProjectOfPublication.latestForDiscovery | dc84f768-e6f2-4eea-b294-6c8ebbd1a156 |