The Role of the Human Nuclear Poly(A) Binding Protein in RNA Decay

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dc.contributor.advisorGreen, Carla B.en
dc.contributor.committeeMemberBuszczak, Michaelen
dc.contributor.committeeMemberLiu, Qinghuaen
dc.contributor.committeeMemberConrad, Nicholasen
dc.creatorBresson, Stefanen
dc.date.accessioned2017-06-02T15:24:57Z
dc.date.available2017-06-02T15:24:57Z
dc.date.created2015-05
dc.date.issued2015-01-26
dc.date.submittedMay 2015
dc.date.updated2017-06-02T15:13:08Z
dc.description.abstractControl of nuclear RNA stability is an important determinant of gene expression, but the factors involved in nuclear RNA decay remain largely unknown in higher eukaryotes. Here, I describe our work showing that polyadenosine (poly(A)) tails can stimulate transcript decay in the nucleus of human cells, a function mediated by the ubiquitous nuclear poly(A) binding protein PABPN1. We show that PABPN1 is required for the degradation of a viral nuclear noncoding RNA as well as an inefficiently exported human mRNA. Importantly, the targeting of RNAs to this decay pathway requires the PABPN1 and poly(A) polymerase (PAP)-dependent extension of the poly(A) tail. Nuclear transcripts with longer poly(A) tails are then selectively degraded by components of the nuclear exosome. I also describe our work showing that PABPN1 and PAP are required for the degradation of a variety of nuclear-retained long noncoding RNAs. Taken together, this work uncovers an important pathway in the turnover of RNAs in the nucleus.en
dc.format.mimetypeapplication/pdfen
dc.identifier.oclc988778236
dc.identifier.urihttps://hdl.handle.net/2152.5/4108
dc.language.isoenen
dc.subjectCell Nucleusen
dc.subjectPoly Aen
dc.subjectPoly(A)-Binding Protein Ien
dc.subjectRNA Stabilityen
dc.titleThe Role of the Human Nuclear Poly(A) Binding Protein in RNA Decayen
dc.typeThesisen
dc.type.materialtexten
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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