| NUP153 is a vertebrate nucleoporin that belongs to the FG repeat–containing family of nuclear pore complex components and forms a major element of the nuclear basket, where it connects the central transport channel to peripheral nuclear structures and defines a key interface between the pore and the genome. The protein displays a modular organization with an N‑terminal region that anchors to the nuclear pore scaffold, a central Zn‑finger–rich segment, and a C‑terminal domain densely packed with FG repeats that interact with transport receptors and other nucleoporins to create a selective environment for macromolecular exchange across the nuclear envelope. Nup153 associates with the nuclear phase of the pore and participates in import and export of multiple cargo classes, including karyopherin‑dependent protein substrates and several classes of RNA, where it contributes to terminal docking steps and release events that shape the directionality and efficiency of nucleocytoplasmic transport. The protein also cooperates with Tpr and other basket nucleoporins to support retention and quality control of specific RNA species, integrating export capacity with surveillance functions that influence which transcripts reach the cytoplasm and at what rate. Nup153 establishes extensive contacts with chromatin and defines large nucleoporin‑associated domains that are enriched for euchromatic features, high RNA polymerase II occupancy, and transcriptionally active genes, linking nuclear pore components to genome‑wide transcriptional programs. These Nup153‑bound regions include clusters on the X chromosome in Drosophila that participate in dosage compensation, where Nup153 function is required for proper activity of the dosage compensation complex and for maintaining enhanced transcription output of X‑linked genes in males. Chromatin association by Nup153 spans genomic segments that range from tens to hundreds of kilobases, creating topological environments that support coordinated expression of gene neighborhoods rather than isolated promoters, and this organization contributes to the maintenance of broad transcriptionally active territories within the nucleus. Perturbation of Nup153 levels alters expression of a large fraction of the genome with pronounced down‑regulation within nucleoporin‑associated regions, demonstrating that this nucleoporin operates as a global transcriptional regulator in addition to its role in transport. |
