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RNA interference knockdown of hU2AF35 impairs cell cycle progression and modulates alternative splicing of Cdc25 transcripts

2006-10Artigo científico Acesso restrito
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dc.contributor.authorPacheco, Teresa
dc.contributor.authorMoita, Luis
dc.contributor.authorGomes, Anita Q.
dc.contributor.authorHacohen, Nir
dc.contributor.authorCarmo-Fonseca, Maria
dc.date.accessioned2021-05-13T10:51:05Z
dc.date.available2021-05-13T10:51:05Z
dc.date.issued2006-10
dc.description© 2006 by The American Society for Cell Biology.pt_PT
dc.description.abstractU2AF is a heterodimeric splicing factor composed of a large (U2AF) and a small (U2AF) subunit. In humans, alternative splicing generates two U2AF variants, U2AF and U2AF. Here, we used RNA interference to specifically ablate the expression of each isoform in HeLa cells. Our results show that knockdown of the major U2AF isoform reduced cell viability and impaired mitotic progression, leading to accumulation of cells in prometaphase. Microarray analysis revealed that knockdown of U2AF affected the expression level of ∼500 mRNAs, from which >90% were underrepresented relative to the control. Among mRNAs underrepresented in U2AF-depleted cells we identified an essential cell cycle gene, Cdc27, for which there was an increase in the ratio between unspliced and spliced RNA and a significant reduction in protein level. Furthermore, we show that depletion of either U2AF or U2AF altered the ratios of alternatively spliced isoforms of Cdc25B and Cdc25C transcripts. Taken together our results demonstrate that U2AF is essential for HeLa cell division and suggest a novel role for both U2AF protein isoforms as regulators of alternative splicing of a specific subset of genes.pt_PT
dc.description.sponsorshipThis work was supported by grants from Fundação para a Ciência e Tecnologia (FCT), Portugal (POCTI/MGI/36547/2000 and POCI/MMO/57700/2004), the Human Frontier Science Program Organization (RG0300/2000-M), and the European Commission (EURASNET). T.R.P. and A.Q.G. were supported by FCT fellowships (PRAXIS XXI/BD/18044/98 and POCTI SFRH/BPD/9388/2002, respectively).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationMol Biol Cell. 2006 Oct;17(10):4187-4199pt_PT
dc.identifier.doi10.1091/mbc.e06-01-0036pt_PT
dc.identifier.eissn1939-4586
dc.identifier.urihttp://hdl.handle.net/10451/47826
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherAmerican Society for Cell Biologypt_PT
dc.relationPOCI/MMO/57700/2004pt_PT
dc.relationGenetic Diseases and RNA Processing
dc.relationPOCTI SFRH/BPD/9388/2002pt_PT
dc.relationANÁLISE IN VIVO DA FUNÇÃO DO FACTOR DE SPLICING U2AF NUM MODELO CELULAR DE VERTEBRADO
dc.relation.publisherversionhttps://www.molbiolcell.org/journal/mbocpt_PT
dc.titleRNA interference knockdown of hU2AF35 impairs cell cycle progression and modulates alternative splicing of Cdc25 transcriptspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumberPOCTI/MGI/36547/2000
oaire.awardNumberPRAXIS XXI/BD/18044/98
oaire.awardTitleGenetic Diseases and RNA Processing
oaire.awardTitleANÁLISE IN VIVO DA FUNÇÃO DO FACTOR DE SPLICING U2AF NUM MODELO CELULAR DE VERTEBRADO
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/POCI/POCTI%2FMGI%2F36547%2F2000/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/POCTI/PRAXIS XXI%2FBD%2F18044%2F98/PT
oaire.citation.endPage4199pt_PT
oaire.citation.issue10pt_PT
oaire.citation.startPage4187pt_PT
oaire.citation.titleMolecular Biology of the Cellpt_PT
oaire.citation.volume17pt_PT
oaire.fundingStreamPOCI
oaire.fundingStreamPOCTI
person.familyNamePacheco
person.familyNameMoita
person.familyNameGomes
person.familyNameCarmo-Fonseca
person.givenNameTeresa
person.givenNameLuis
person.givenNameAnita
person.givenNameMaria
person.identifier335918
person.identifier.ciencia-idCA1C-AE28-33FE
person.identifier.ciencia-id4B10-E015-52B7
person.identifier.ciencia-idB31F-0435-0753
person.identifier.orcid0000-0002-5506-0233
person.identifier.orcid0000-0003-0707-315X
person.identifier.orcid0000-0002-3348-0448
person.identifier.orcid0000-0002-3402-7143
person.identifier.ridL-1296-2013
person.identifier.ridC-3580-2014
person.identifier.scopus-author-id24554088300
person.identifier.scopus-author-id7202386033
person.identifier.scopus-author-id7007128195
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
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