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Perspective in Alternative Splicing Coupled to Nonsense-Mediated mRNA Decay

2020-12-10Journal article Open access
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dc.contributor.authorGarcía-Moreno, Juan
dc.contributor.authorRomão, Luísa
dc.date.accessioned2021-03-09T17:53:40Z
dc.date.available2021-03-09T17:53:40Z
dc.date.issued2020-12-10
dc.descriptionReviewpt_PT
dc.description.abstractAlternative splicing (AS) of precursor mRNA (pre-mRNA) is a cellular post-transcriptional process that generates protein isoform diversity. Nonsense-mediated RNA decay (NMD) is an mRNA surveillance pathway that recognizes and selectively degrades transcripts containing premature translation-termination codons (PTCs), thereby preventing the production of truncated proteins. Nevertheless, NMD also fine-tunes the gene expression of physiological mRNAs encoding full-length proteins. Interestingly, around one third of all AS events results in PTC-containing transcripts that undergo NMD. Numerous studies have reported a coordinated action between AS and NMD, in order to regulate the expression of several genes, especially those coding for RNA-binding proteins (RBPs). This coupling of AS to NMD (AS-NMD) is considered a gene expression tool that controls the ratio of productive to unproductive mRNA isoforms, ultimately degrading PTC-containing non-functional mRNAs. In this review, we focus on the mechanisms underlying AS-NMD, and how this regulatory process is able to control the homeostatic expression of numerous RBPs, including splicing factors, through auto- and cross-regulatory feedback loops. Furthermore, we discuss the importance of AS-NMD in the regulation of biological processes, such as cell differentiation. Finally, we analyze interesting recent data on the relevance of AS-NMD to human health, covering its potential roles in cancer and other disorders.pt_PT
dc.description.sponsorshipThis work was partially supported by UID/MULTI/04046/2019 Research Unit grant from Fundação para a Ciência e a Tecnologia (FCT), Portugal (to BioISI). J.F.G.-M. is recipient of a fellowship from BioSys PhD programme PD65-2012 (Ref SFRH/PD/BD/142898/2018) from FCT.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationInt J Mol Sci. 2020 Dec 10;21(24):9424. doi: 10.3390/ijms21249424pt_PT
dc.identifier.doihttps://doi.org/10.3390/ijms21249424pt_PT
dc.identifier.issn1661-6596
dc.identifier.urihttp://hdl.handle.net/10400.18/7381
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationSFRH/PD/BD/142898/2018pt_PT
dc.relation.publisherversionhttps://www.mdpi.com/1422-0067/21/24/9424pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectAS-NMDpt_PT
dc.subjectAlternative Splicing (AS)pt_PT
dc.subjectGene Expression Regulationpt_PT
dc.subjectNonsense-mediated RNA Decay (NMD).pt_PT
dc.subjectDoenças Genéticaspt_PT
dc.subjectGenómica Funcional e Estruturalpt_PT
dc.titlePerspective in Alternative Splicing Coupled to Nonsense-Mediated mRNA Decaypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FMulti%2F04046%2F2013/PT (2019)
oaire.citation.issue24pt_PT
oaire.citation.startPage9424pt_PT
oaire.citation.titleInternational Journal of Molecular Sciencespt_PT
oaire.citation.volume21pt_PT
oaire.fundingStream5876
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.embargofctAcesso de acordo com página web do editor da revista.pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication0dbd968f-ea65-4a2a-9b40-008aff7adbeb
relation.isProjectOfPublication.latestForDiscovery0dbd968f-ea65-4a2a-9b40-008aff7adbeb

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