Publication
More than just scanning: the importance of cap-independent mRNA translation initiation for cellular stress response and cancer
| dc.contributor.author | Lacerda, Rafaela | |
| dc.contributor.author | Menezes, Juliane | |
| dc.contributor.author | Romão, Luísa | |
| dc.date.accessioned | 2017-03-02T12:45:49Z | |
| dc.date.available | 2017-03-02T12:45:49Z | |
| dc.date.issued | 2016-12-02 | |
| dc.description.abstract | The scanning model for eukaryotic mRNA translation initiation states that the small ribosomal subunit, along with initiation factors, binds at the cap structure at the 5' end of the mRNA and scans the 5' untranslated region (5'UTR) until an initiation codon is found. However, under conditions that impair canonical cap-dependent translation, the synthesis of some proteins is kept by alternative mechanisms that are required for cell survival and stress recovery. Alternative modes of translation initiation include cap- and/or scanning-independent mechanisms of ribosomal recruitment. In most cap-independent translation initiation events there is a direct recruitment of the 40S ribosome into a position upstream, or directly at, the initiation codon via a specific internal ribosome entry site (IRES) element in the 5'UTR. Yet, in some cellular mRNAs, a different translation initiation mechanism that is neither cap- nor IRES-dependent seems to occur through a special RNA structure called cap-independent translational enhancer (CITE). Recent evidence uncovered a distinct mechanism through which mRNAs containing N 6-methyladenosine (m6A) residues in their 5'UTR directly bind eukaryotic initiation factor 3 (eIF3) and the 40S ribosomal subunit in order to initiate translation in the absence of the cap-binding proteins. This review focuses on the important role of cap-independent translation mechanisms in human cells and how these alternative mechanisms can either act individually or cooperate with other cis-acting RNA regulons to orchestrate specific translational responses triggered upon several cellular stress states, and diseases such as cancer. Elucidation of these non-canonical mechanisms reveals the complexity of translational control and points out their potential as prospective novel therapeutic targets. | pt_PT |
| dc.description.sponsorship | This work was partially supported by Fundação para a Ciência e a Tecnologia (UID/MULTI/04046/2013 to BioISI from FCT/MCTES/PIDDAC). Rafaela Lacerda and Juliane Menezes were supported by fellowships from Fundação para a Ciência e a Tecnologia (SFRH/BD/74778/2010 and SFRH/BPD/98360/2013, respectively). | pt_PT |
| dc.description.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.citation | ell Mol Life Sci. 2017 May;74(9):1659-1680. doi: 10.1007/s00018-016-2428-2. Epub 2016 Dec 2. | pt_PT |
| dc.identifier.doi | 10.1007/s00018-016-2428-2 | pt_PT |
| dc.identifier.issn | 1420-682X | |
| dc.identifier.uri | http://hdl.handle.net/10400.18/4394 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.publisher | Springer Verlag/Birkhäuser Basel | pt_PT |
| dc.relation.publisherversion | https://link.springer.com/article/10.1007%2Fs00018-016-2428-2 | pt_PT |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt_PT |
| dc.subject | Cancer | pt_PT |
| dc.subject | Cellular Stress | pt_PT |
| dc.subject | Cis-acting RNA Regulons | pt_PT |
| dc.subject | Disease | pt_PT |
| dc.subject | Eukaryotic Translation Initiation | pt_PT |
| dc.subject | Non-canonical Translation Initiation | pt_PT |
| dc.subject | Repression of Global Protein Synthesis | pt_PT |
| dc.subject | Expressão Génica | pt_PT |
| dc.subject | Genómica Funcional e Estrutural | pt_PT |
| dc.title | More than just scanning: the importance of cap-independent mRNA translation initiation for cellular stress response and cancer | 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.endPage | 22 | pt_PT |
| oaire.citation.startPage | 1 | pt_PT |
| oaire.citation.title | Cellular and Molecular Life Sciences | 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 |