RNA association defines a functionally conserved domain in the nuclear pore protein Nup153

Traffic between the nucleus and cytoplasm takes place through a macromolecu lar structure termed the nuclear pore complex. To understand how the vital process of nucleocytoplasmic transport occurs, the contribution of individu al pore proteins must be elucidated. One such protein, the nucleoporin Nup1 53, is localized to the nuclear basket of the pore complex and has been sho wn to be a central component of the nuclear transport machinery. Perturbati on of Nup153 function was demonstrated previously to block the export of se veral 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 do main within Nup153, encompassing amino acids 250-400 in human Nup153, that is responsible for RNA association. After cloning this region of Xenopus Nu p153, 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 pr operty is a hallmark feature of Nup153 and pointing toward a subset of amin o acid residues that are key to conferring this ability. We have further de termined 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 R NA binding in Nup153 function at the nuclear pore.