Nuclear export dynamics of RNA–protein complexes (original) (raw)

The central dogma of molecular biology-DNA makes RNA makes proteins-is a flow of information that in eukaryotes encounters a physical barrier: the nuclear envelope, which encapsulates, organizes and protects the genome. Nuclear-pore complexes, embedded in the nuclear envelope, regulate the passage of molecules to and from the nucleus, including the poorly understood process of the export of RNAs from the nucleus. Recent imaging approaches focusing on single molecules have provided unexpected insight into this crucial step in the information flow. This review addresses the latest studies of RNA export and presents some models for how this complex process may work. Since its first description in electron micrographs 1 , our understanding of the nuclear-pore complex (NPC), arguably the largest nanomachine in the cell, has increased steadily. We are now at the point where we have a comprehensive overview of the NPC components and their contribution to its structure, as well as initial insights into the mechanism of NPC assembly and a sound understanding of the principal functions of the NPC 2. The 100-nm diameter NPC has a core structure consisting of a hollow cylinder embedded in the nuclear envelope, which displays an eight-fold symmetry of about 30 different proteins termed nucleoporins (Nups). The NPC acts as the gateway between the nucleus and the cytoplasm; only those macromolecules carrying specific import and export signals are permitted to pass through the central channel of the NPC, although water and metabolites can pass through freely 3,4. The NPC consists of several major domains (Fig. 1): the selective central channel, or central transporter region; the core scaffold that supports the central channel; the transmembrane regions; the nuclear basket; and the cytoplasmic filaments 5. The central channel is filled and surrounded with a distinct class of Nup that has numerous large domains rich in phenylalanine and glycine repeats, termed FG Nups. It is this central channel and the FG Nups that seem sufficient to mediate selective receptor-mediated transport 6,7. The nuclear basket consists of eight filaments that reach into the nucleoplasm, attached to each other by a ring at the end. Electron microscopy tomographs have shown that filaments extend from this basket into the nucleus 8,9. The cytoplasmic filaments are less ordered, forming highly mobile molecular rods projecting into the cytoplasm. The reach of NPCs can extend about 100 nm into the nucleus and cytoplasm 10,11 .