The role of phase separation for RNA and protein transport through the nuclear pore complex

Eukaryotes developed a separate compartment for transcription, the nucleus (karyon), which is protected by a double membrane with micropores that enable the exchange of solutes between cytoplasm and nucleoplasm, in particular the exchange of RNAs and proteins. The composition and structure of the nuclear pore core scaffold have been resolved at the atomic level. The core of the transport mechanism is generated by intrinsically disordered phenylalanine-glycine (FG)-repeat proteins, the FG-nucleoporins. The in vivo state of the FG barrier in native nuclear pore complexes (NPCs) remains a topic of debate, with polymer brushes, liquid state, or bimolecular condensates (also termed hydrogels) discussed as barriers in the pore. Purified FG domains can reproduce many of the features of nuclear transport, such as the dependence of cargo transport on size and certain surface features. This review provides an overview of the composition, structure, and transport mechanism of NPCs and the role of phase separation. Due to analogous functions in protein and RNA transport and similarities of transport properties through NPCs and plasmodesmata, the summary provided here for the NPCs may be instructive for studies on the structure and function of plasmodesmata.