Models of normal interphase NPC assembly and defective NPC biogenesis resulting from Torsin manipulation. (A) Following mitosis, NPC assembly occurs via an inside-out evagination of the INM in a process that requires the recruitment of POM121. Nuclear ring components and NPC subcomplexes are shuttled through mature pores previously assembled through a postmitotic insertion mechanism. As pore intermediates mature, Nups that presumably deform the membrane evagination are added in a process that drives the growth of the complex both laterally and toward the ONM (intermediate I). Following a membrane fusion event, late-stage and cytoplasmic Nups like Nup358 are added (intermediate II), ultimately giving rise to a complete NPC (III). (B) The formation of NE aberrations resulting from defective interphase assembly of NPCs upon Torsin manipulation or depletion. Interphase assembly begins in a POM121-dependent manner, and pore intermediates mature to a stage that precedes membrane fusion (intermediate I). MLF2 is recruited early in the biogenesis of NE herniations, likely during the recruitment of early stage Nups, and is enriched in the lumen of the mature herniation. The INM proximal to the ONM expands to give rise to an omega-shaped herniation of the NE (intermediate II). Specific protein components of the herniations including MLF2 are then labeled with K48-Ub chains (intermediate III). These structures are static through interphase and are turned over at the onset of mitosis.