The conserved Sac3:Thp1:Sem1:Sus1:Cdc31 (TREX2) complex binds to nuclear pore 
complexes (NPCs) and, in addition to integrating mRNA nuclear export with 
preceding steps in the gene expression pathway, facilitates re-positioning of 
highly regulated actively transcribing genes (such as GAL1) to NPCs. Although 
TREX2 is thought to bind NPC protein Nup1, defining the precise role of this 
interaction has been frustrated by the complex pleiotropic phenotype exhibited 
by nup1Δ strains. To provide a structural framework for understanding the 
binding of TREX2 to NPCs and its function in the gene expression pathway, we 
have determined the structure of the Nup1:TREX2 interaction interface and used 
this information to engineer a Sac3 variant that impairs NPC binding while not 
compromising TREX2 assembly. This variant inhibited the NPC association of both 
de-repressed and activated GAL1 and also produced mRNA export and growth 
defects. These results indicate that the TREX2:Nup1 interaction facilitates the 
efficient nuclear export of bulk mRNA together with the re-positioning of GAL1 
to NPCs that is required for transcriptional control that is mediated by removal 
of SUMO from repressors by NPC-bound Ulp1.