Nup153 is an M9-containing mobile nucleoporin with a novel Ran-binding domain

We employed a phage display system to search for proteins that interact wit h transportin 1 (TRN1), the import receptor for shuttling hnRNP proteins wi th an M9 nuclear localization sequence (NLS), and identified a short region within the N-terminus of the nucleoporin Nup153 which binds TRN1, Nup153 i s located at the nucleoplasmic face of the nuclear pore complex (NPC), in t he distal basket structure, and functions in mRNA export. We show that this Nup153 TRN1-interacting region is an M9 NLS, We found that both import and export receptors interact with several regions of Nup153, in a RanGTP-regu lated fashion, RanGTP dissociates Nup153-import receptor complexes, but is required for Nup153-export receptor interactions. We also show that Nup153 is a RanGDP-binding protein, and that the interaction is mediated by the zi nc finger region of Nup153, This represents a novel Ran-binding domain, whi ch we term the zinc finger Ran-binding motif, We provide evidence that Nup1 53 shuttles between the nuclear and cytoplasmic faces of the NPC, The prese nce of an M9 shuttling domain in Nup153, together with its ability to move within the NPC and to interact with export receptors, suggests that this nu cleoporin is a mobile component of the pore which carries export cargos tow ards the cytoplasm.