Traffic between the nucleus and cytoplasm takes place through a macromolecular 
structure termed the nuclear pore complex. To understand how the vital process 
of nucleocytoplasmic transport occurs, the contribution of individual pore 
proteins must be elucidated. One such protein, the nucleoporin Nup153, is 
localized to the nuclear basket of the pore complex and has been shown to be a 
central component of the nuclear transport machinery. Perturbation of Nup153 
function was demonstrated previously to block the export of several classes of 
RNA cargo. Moreover, these studies also showed that Nup153 can stably associate 
with RNA in vitro. In this study, we have mapped a domain within Nup153, 
encompassing amino acids 250-400 in human Nup153, that is responsible for RNA 
association. After cloning this region of Xenopus Nup153, we performed a 
cross-species analysis. Despite variation in sequence conservation between 
Drosophila, Xenopus, and human, this domain of Nup153 displayed robust RNA 
binding activity in each case, indicating that this property is a hallmark 
feature of Nup153 and pointing toward a subset of amino acid residues that are 
key to conferring this ability. We have further determined that a recombinant 
fragment of Nup153 can bind directly to RNA and that this fragment can interact 
with endogenous RNA targets. Our findings identify a functionally conserved 
domain in Nup153 and suggest a role for RNA binding in Nup153 function at the 
nuclear pore.