Green, Carla B.2017-06-022017-06-022015-052015-01-26May 2015https://hdl.handle.net/2152.5/4108Control 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.application/pdfenCell NucleusPoly APoly(A)-Binding Protein IRNA StabilityThesis2017-06-02988778236