Nucleus and cytoplasm are physically separated by a semipermeable barrier known as the nuclear envelope. Due to this compartmentalization, a large number of macromolecules traverse the nuclear envelope to reach their biological destination. For example, proteins are synthesized by ribosomes in the cytoplasm, but some of them such as polymerases, transcription factors, nucleosome components and splicing factors, have to traverse the NPC to reach the nucleoplasm. Conversely, all RNA species are transcribed and processed in the nucleus and later, most of mature RNAs are exported through the NPC to the cytoplasm, where their biological roles take place. Therefore, the regulation of RNA and protein trafficking between nucleus and cytoplasm directly impacts on gene expression [163, 164] . NPC forms large structures (∼125 MDa) embedded in the nuclear envelope with a polarized eightfold symmetrical core. It is sandwiched by a cytoplasmic and nuclear ring, which projects eight filaments of about 50 nm into the cytoplasm and a basket-like structure of about 100 nm into the nucleoplasm [165, 166] . The NPC is composed of multiple copies (8, 16 or 32) of ∼30 different proteins, called Nups, that are grouped in three major classes: (i) the phenylalanineglycine (FG)-containing nucleoporins that actively work in the nuclear-cytoplasmic trafficking of macromolecules; (ii) the structural components, which lack FG-rich domains and (iii) the membrane integral proteins, which anchor the NPC to the nuclear envelope [163, 167] . Whereas the two last groups of nucleoporins play a role in the architecture and localization of the NPC, the FG-nucleoporins directly regulate the transport of RNAs and proteins through the NPC, and they are the main nucleoporin class targeted by viruses (Figure 4) .