Combinatorial Regulation of Signal-Induced CD45 Exon Repression by hnRNP L and PSF

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dc.contributor.advisorLynch, Kristen W.en
dc.creatorMelton, Alexis Allysonen
dc.date.accessioned2010-07-12T18:47:46Z
dc.date.available2010-07-12T18:47:46Z
dc.date.issued2007-08-08
dc.description.abstractCD45 is a hematopoetic-specific tyrosine phoshatase. In resting T cells three variable exons are partially repressed, and following antigen challenge, these exons are more highly repressed. Previous work identified the ESS1 silencer element that functions to mediate exon 4 silencing under resting conditions by binding to hnRNP L. ESS1 is also sufficient to confer the activation-induced increase in exon repression, and this document describes two mechanisms responsible for mediating this effect. First, hnRNP L silencing function is slightly increased in activated cells as compared to resting cells. Additionally, PSF binds to the ESS1 complex in a signal-dependent manner and provides a significant increase in repressive activity. Further investigation shows these two mechanisms are largely independent but show some functional crosstalk, and while neither of these mechanisms is sufficient in isolation, the combination of these two effects accounts for an increase in exon silencing that is of similar magnitude to the total observed change in splicing in response to cellular activation.en
dc.format.digitalOriginborn digitalen
dc.format.mediumElectronicen
dc.format.mimetypeapplication/pdfen
dc.identifier.oclc664097816
dc.identifier.urihttps://hdl.handle.net/2152.5/662
dc.language.isoenen
dc.subjectHeterogeneous-Nuclear Ribonucleoproteinsen
dc.subjectRNA Splicingen
dc.subjectRepressor Proteinsen
dc.titleCombinatorial Regulation of Signal-Induced CD45 Exon Repression by hnRNP L and PSFen
dc.typeThesisen
dc.type.genredissertationen
dc.type.materialTexten
thesis.date.available2008-08-08
thesis.degree.departmentGraduate School of Biomedical Sciencesen
thesis.degree.disciplineBiological Chemistryen
thesis.degree.grantorUT Southwestern Medical Centeren
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen

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