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dc.contributor.authorYang, Zheqiong
dc.contributor.authorSui, Yang
dc.contributor.authorXiong, Shiqin
dc.contributor.authorLiour, Sean S
dc.contributor.authorPhillips, Andrew C
dc.contributor.authorKo, Lan
dc.date.accessioned2010-09-24T22:03:27Z
dc.date.available2010-09-24T22:03:27Z
dc.date.issued2007-04-23en_US
dc.identifier.citationNucleic Acids Res. 2007 Mar 1; 35(6):1919-1932en_US
dc.identifier.issn1362-4962en_US
dc.identifier.pmid17337438en_US
dc.identifier.doi10.1093/nar/gkl1092en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/147
dc.description.abstractAlternative splicing produces functionally distinct proteins participating in cellular processes including differentiation and development. CoAA is a coactivator that regulates transcription-coupled splicing and its own pre-mRNA transcript is alternatively spliced. We show here that the CoAA gene is embryonically expressed and alternatively spliced in multiple tissues to three splice variants, CoAA, CoAM and CoAR. During retinoic-acid-induced P19 stem cell differentiation, the expression of CoAA undergoes a rapid switch to its dominant negative splice variant CoAM in the cavity of the embryoid body. CoAM functionally inhibits CoAA, and their switched expression up-regulates differentiation marker Sox6. Using a CoAA minigene cassette, we find that the switched alternative splicing of CoAA and CoAM is regulated by the cis-regulating sequence upstream of the CoAA basal promoter. Consistent to this, we show that p54(nrb) and PSF induce CoAM splice variant through the cis-regulating sequence. We have previously shown that the CoAA gene is amplified in human cancers with a recurrent loss of this cis-regulating sequence. These results together suggest that the upstream regulatory sequence contributes to alternative splicing of the CoAA gene during stem cell differentiation, and its selective loss in human cancers potentially deregulates CoAA alternative splicing and alters stem cell differentiation.
dc.rightsThe PMC Open Access Subset is a relatively small part of the total collection of articles in PMC. Articles in the PMC Open Access Subset are still protected by copyright, but are made available under a Creative Commons or similar license that generally allows more liberal redistribution and reuse than a traditional copyrighted work. Please refer to the license statement in each article for specific terms of use. The license terms are not identical for all articles in this subset.en_US
dc.subject.meshAlternative Splicingen_US
dc.subject.meshAmino Acid Sequenceen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshCarcinoma, Embryonal / genetics / metabolismen_US
dc.subject.meshCell Differentiationen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshDNA-Binding Proteins / biosynthesisen_US
dc.subject.meshEmbryonic Stem Cells / metabolismen_US
dc.subject.meshGene Expression Regulation, Developmentalen_US
dc.subject.meshGene Expression Regulation, Neoplasticen_US
dc.subject.meshHigh Mobility Group Proteins / biosynthesisen_US
dc.subject.meshMiceen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshNuclear Matrix-Associated Proteins / metabolismen_US
dc.subject.meshOncogene Proteins / genetics / metabolismen_US
dc.subject.meshRNA-Binding Proteins / metabolismen_US
dc.subject.meshRegulatory Elements, Transcriptionalen_US
dc.subject.meshSOXD Transcription Factorsen_US
dc.subject.meshTranscription Factors / biosynthesis / genetics / metabolismen_US
dc.titleSwitched alternative splicing of oncogene CoAA during embryonal carcinoma stem cell differentiation.en_US
dc.typeJournal Articleen_US
dc.typeResearch Support, Non-U.S. Gov'ten_US
dc.identifier.pmcidPMC1874587en_US
dc.contributor.corporatenameDepartment of Pathologyen_US
refterms.dateFOA2019-04-09T16:27:31Z
html.description.abstractAlternative splicing produces functionally distinct proteins participating in cellular processes including differentiation and development. CoAA is a coactivator that regulates transcription-coupled splicing and its own pre-mRNA transcript is alternatively spliced. We show here that the CoAA gene is embryonically expressed and alternatively spliced in multiple tissues to three splice variants, CoAA, CoAM and CoAR. During retinoic-acid-induced P19 stem cell differentiation, the expression of CoAA undergoes a rapid switch to its dominant negative splice variant CoAM in the cavity of the embryoid body. CoAM functionally inhibits CoAA, and their switched expression up-regulates differentiation marker Sox6. Using a CoAA minigene cassette, we find that the switched alternative splicing of CoAA and CoAM is regulated by the cis-regulating sequence upstream of the CoAA basal promoter. Consistent to this, we show that p54(nrb) and PSF induce CoAM splice variant through the cis-regulating sequence. We have previously shown that the CoAA gene is amplified in human cancers with a recurrent loss of this cis-regulating sequence. These results together suggest that the upstream regulatory sequence contributes to alternative splicing of the CoAA gene during stem cell differentiation, and its selective loss in human cancers potentially deregulates CoAA alternative splicing and alters stem cell differentiation.


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