Structure and Function of the Nuclear Pore Complex Cytoplasmic mRNA Export Platform

Highlights

• Integrative structure at 9 Å precision of the endogenous Nup82 holo-complex

• Molecular architecture of the conserved 1.8-MDa cytoplasmic mRNA export platform

• Structural framework to understand the mRNP remodeling and export processes

• mRNP remodeling machinery is positioned over the NPC’s central channel, not in filaments

Summary

The last steps in mRNA export and remodeling are performed by the Nup82 complex, a large conserved assembly at the cytoplasmic face of the nuclear pore complex (NPC). By integrating diverse structural data, we have determined the molecular architecture of the native Nup82 complex at subnanometer precision. The complex consists of two compositionally identical multiprotein subunits that adopt different configurations. The Nup82 complex fits into the NPC through the outer ring Nup84 complex. Our map shows that this entire 14-MDa Nup82-Nup84 complex assembly positions the cytoplasmic mRNA export factor docking sites and messenger ribonucleoprotein (mRNP) remodeling machinery right over the NPC’s central channel rather than on distal cytoplasmic filaments, as previously supposed. We suggest that this configuration efficiently captures and remodels exporting mRNP particles immediately upon reaching the cytoplasmic side of the NPC.