Molecular Architecture of the Nup82 Complex, the Cytoplasmic mRNA Export Platform in the Nuclear Pore Complex

Abstract

mRNA biogenesis is an essential and intricate process that occurs within the nucleus and ends with the mRNA export through the nuclear pore complex (NPC), a conserved process which defects lead to serious human diseases. The protein assemblies that perform the last steps in mRNA export are located at the cytoplasmic face of the Nuclear Pore complex (NPC). Here we describe the molecular architecture of the NPC cytoplasmic mRNA export machinery. Through an integrative modeling approach that combines various sources of data, including chemical cross-linking, electron microscopy, and small angle X-ray scattering, we generate a hybrid structure of the native Nup82 complex, the main component of the assembly. Correlative phenotypic mapping and structural data from chemical cross-linking reveal how the Nup82 complex docks into the Nup84 complex at the cytoplasmic face of the NPC and allows us to generate a first map of the associated mRNA remodeling machinery. Our map serves as a framework to understand the mRNA export process and NPC function.