In eukaryotic cells, RNA biogenesis and DNAreplication take place within the nucleus andare separate from the cytoplasmic machinery for protein synthesis. As a consequence messenger RNAs, ribosomal RNAs, tRNAs and all cytoplasmic RNAs from nuclear origin need to be transported from their site of synthesis in the nucleus to their final cytoplasmic destination. NPCs are large proteinaceous structures that form aqueous channels across the nuclear envelope. NPCs are composed of multiple copies of up to about 50 to 100 polypeptides termed nucleoporins. The repeated domains of nucleoporins interact with multiple nuclear transport receptors and have been proposed to provide an interaction surface during translocation of receptor-cargo complexes through the central aqueous channel of the pore.
Nuclear export is mediated by saturable receptors that shuttle between nucleus and cytoplasm.
The Nuclear Export Signal of the RNP can be based on the RNA molecule or on some of the RNA binding proteins, or be a composite of the two. RNA binding proteins bearing an NES are defined as adaptors, as they provide a link between the RNA and the export receptor. Exportin-t, the tRNA export receptor, is the sole case so far of an export receptor which directly interacts with the RNA, without an adaptor protein. Upon binding, the export receptors dock their RNP-cargoes to the NPC and facilitate their translocation across the central channel of the pore. On the cytoplasmic side of the NPC, the exported RNP is released and the receptor returns to the nucleoplasm, without the cargo, to initiate additional rounds of export.