PRJNA548782
DLD-1 cells Ser5P Pol II ChIP-Seq after Tpr Depletion
The basket of the nuclear pore complex (NPC) is important for many processes beyond nucleocytoplasmic trafficking, including protein modification, chromatin remodeling, transcription, mRNA processing, mRNA export. The multi-faceted nature of NPCs and the slow turnover of their components has made it difficult to understand the role of basket nucleoporins (Nup153, Nup50 and Tpr) in these diverse processes. To address this question, we used an Auxin-Induced Degron (AID) system to distinguish roles of basket nucleoporins: Loss of individual nucleoporins caused distinct alterations of nucleocytoplasmic trafficking patterns and dramatically different impacts on gene expression. Importantly, Tpr elimination caused rapid and profound changes in transcriptomic profiles within two hours of auxin addition. These changes were dissimilar to shifts observed after loss of Nup153 or Nup50, but closely related to changes after depletion of transport factor NXF1 or the GANP subunit of the TRanscription-EXport-2 (TREX-2) mRNA export complex. Moreover, NPC association of GANP was specifically disrupted upon TPR depletion. Together, our findings demonstrate a unique and pivotal role of Tpr in regulating gene expression through GANP and/or NXF1 dependent mRNA export.