A fundamental question in cell biology is the mechanism by which one structure, the nuclear pore complex, controls all trafficking between the nucleus and the cytoplasm of the eukaryotic cell. Despite this vitally important function, much of the composition of the pores of higher eukaryotes remains unknown, and the molecular mechanism by which the pore engages and translocates substrates is still not understood. Significant progress has been made recently in understanding interactions between pore components and soluble transport factors during import into the nucleus. In contrast, progress is just beginning in the study of factors required for RNA export The Xenopus laevis model provides a uniquely powerful system in which to study RNA export. Using this system, I have shown that the nuclear pore protein, Nup98, is an essential component of multiple RNA export pathways. Additionally, Nup98 specifically interacts with a second protein, Gle2; genetic evidence has linked mutations in the homologs of each of these proteins to defects in polyA+ mRNA export in yeast. The central hypothesis behind this proposal is that the Nup98/Gle2 complex is a key mediator of nuclear export, providing a primary binding site to link export substrates to the transport machinery of the pore. The goals address the specific associations formed by this one subcomplex of the nuclear pore; however it is expected that understanding of this critical interaction will advance our knowledge of the mechanism of nuclear export and provide a framework for characterizing interactions between other export factors and the nuclear pore. The long term goal of this work is a full understanding of how export from the nucleus is conducted through precise cooperation between soluble proteins and the nuclear pore complex.
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