Protein import into the nucleus: An integrated view

The directed movement of macromolecules into and out of the nucleus is a fundamental process in eukaryotes and occurs through the nuclear pore complex (NPC). A diverse array of molecules are transported across the nuclear envelope including proteins, mRNAs, tRNAs, snRNP complexes, ribosomal subunits, and in specialized cases, DNA. The structural and functional differences between these molecules point to the mechanistic complexity of NPCs and other components of the nuclear transport apparatus. This machinery must not only recognize within transported molecules specific targeting signals that differ between proteins, RNA, and RNA/protein complexes, it must translocate these molecules across the nuclear envelope. Additional levels of complexity are necessary because molecules such as proteins may continually undergo bidirectional transport across the envelope. Beyond these basic functions, the nuclear transport apparatus is regulated at the level of individual substrates and at more global levels such as coupling to cell cycle progression.