Nup153 is a large (153 kD) O-linked glyco-protein which is a component of the 
basket structure located on the nucleoplasmic face of nuclear pore complexes. 
This protein exhibits a tripartite structure consisting of a zinc finger domain 
flanked by large (60-70 kD) NH2- and COOH-terminal domains. When full-length 
human Nup153 is expressed in BHK cells, it accumulates appropriately at the 
nucleoplasmic face of the nuclear envelope. Targeting information for Nup153 
resides in the NH2-terminal domain since this region of the molecule can direct 
an ordinarily cytoplasmic protein, pyruvate kinase, to the nuclear face of the 
nuclear pore complex. Overexpression of Nup153 results in the dramatic 
accumulation of nuclear poly (A)+ RNA, suggesting an inhibition of RNA export 
from the nucleus. This is not due to a general decline in nucleocytoplasmic 
transport or to occlusion or loss of nuclear pore complexes since nuclear 
protein import is unaffected. While overexpression of certain Nup153 constructs 
was found to result in the formation of unusual intranuclear membrane arrays, 
this structural phenotype could not be correlated with the effects on poly (A)+ 
RNA distribution. The RNA trafficking defect was, however, dependent upon the 
Nup153 COOH-terminal domain which contains most of the XFXFG repeats. It is 
proposed that this region of Nup153, lying within the distal ring of the nuclear 
basket, represents a docking site for mRNA molecules exiting the nucleus.