Nuclear pore complexes (NPCs) are large structures composed of diverse nucleoporins (Nups) that allow the diffusion of molecules into and out of the nucleus. Assisted diffusion is facilitated by transport factors, but passive diffusion depends on the size of the translocating molecule. Nups can determine pore size, but it is still unknown how their variation and the resulting physical properties of NPCs can modulate transcriptional pathways. Now, Tadashi Makio and Richard Wozniak (Makio and Wozniak, 2020) report that in yeast, Nup170 controls the transcription of genes that are dependent on the Spt–Ada–Gcn5 acetyltransferase (SAGA) complex through regulating the passive diffusion of macromolecules. In Nup170 mutants, the expression of SAGA-dependent genes is downregulated owing to impaired assembly of preinitiation complexes (PICs), which include the SAGA complex. The SAGA component Spt 7 can be cleaved by the vacuolar protease Pep4, leading to increased levels of the SAGA-like (SLIK) complexes. As shown here, depletion of Nup170 leads to an imbalance between available SAGA and SLIK complexes; this results from an increase in the passive diffusion of Pep4 into the nucleus, as determined by analysis of newly generated Pep4 reporters. Interestingly, the authors observe similar results in stressed wild-type cells, in which NPC permeability is similarly increased. This study thus unravels a new function for Nup170 in controlling gene expression by modulating the NPC-diffusion barrier.
- © 2020. Published by The Company of Biologists Ltd