Role for RNA association in the function of the nuclear pore protein Nup153

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Title Role for RNA association in the function of the nuclear pore protein Nup153
Publication Type dissertation
School or College School of Medicine
Department Oncological Sciences
Author Dimaano, Christian
Date 2004-05
Description Communication between the nucleus and the cytoplasm is dependent upon transport across the double membrane of the nuclear envelope. All traffic between the nucleus and cytoplasm occurs at large proteinacious structures embedded within the nuclear envelope called nuclear pore complexes (NPCs). Trafficking of a wide array of cargo necessitates that individual pore proteins coordinately function with localization signals, receptors, and accessory factors to mediate propel-transport events. Although much is known about the soluble machinery that is required for nucleocytoplasmic transport, little is known about how individual nucleoporins contribute to this process. One nucleoporin, Nup153, is a central regulator of transport. Overexpression of a C-terminal fragment of Nup153 in cultured cells causes the accumulation of poly(A)+ RNA in the nucleus, suggesting a role for Nup153 in mRNA export. Moreover, specific perturbation of Nup153 in vivo results in the prevention of several classes of RNA, including mRNA, from being exported. The goal of this dissertation is to define how the property of RNA association contributes to the function of this pore protein. I have examined the interaction of Nup153 with RNA and identified a novel RNA binding domain within this pore protein that is sufficient to mediate this property. My studies indicate an important functional attribute of RNA association, as this domain is functionally conserved through evolution. I have also assisted in further characterizing Nup153's RNA binding properties and we have found that Nup153 shows a preference for single-stranded RNAs that lack structure. Unstructured stretches of single-stranded RNA are defined to be mRNA identity elements and raise the possibility that the RNA binding domain of Nup153 acts as an interface with mRNA. To better define the RNA determinants that mediate Nup153 recognition, we have established minimal length and base composition requirements. Our findings show for the first time that binding of RNA substrates by a nucleoporin can be correlated with nuclear export. In addition, I contributed to a project focused on Nup153 nuclear mobility and we found that dynamics of this pore protein in the nucleus is dependent upon on-going transcription, supporting a connection between Nup153 function and mRNA production.
Type Text
Publisher University of Utah
Subject Nucleoporin; RNA Binding
Subject MESH RNA, Messenger; Membrane Proteins; Biological Transport
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "A role for RNA association in the function of the nuclear pore protein Nup153.." Spencer S. Eccles Health Sciences Library. Print version of "A role for RNA association in the function of the nuclear pore protein Nup153.." available at J. Willard Marriott Library Special Collection. QP6.5 2004 .D55.
Rights Management © Christian Dimaano.
Format application/pdf
Format Medium application/pdf
Format Extent 3,433,337 bytes
Identifier undthes,4786
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
Master File Extent 3,433,393 bytes
ARK ark:/87278/s6nk3gvd
Setname ir_etd
ID 191252
Reference URL https://collections.lib.utah.edu/ark:/87278/s6nk3gvd
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