The basic mechanism of nucleocytoplasmic transport. (a) The Ran GTPase cycle. Ran can bind either (GDP) or (GTP). The intrinsic GTPase activity of Ran is activated by the concerted action of the (GAP) and the Ran‐binding protein 1 (RanBP1). These proteins are localized in the cytoplasm. Thus, Ran would be mainly in the GDP‐bound form in this compartment. The conversion of RanGDP into RanGTP requires the guanine nucleotide exchange factor (GEF or RCC1). As RanGEF is nuclear, Ran is likely to be bound to GTP in this compartment. The size of the circles around Ran reflect the relative concentration of the different forms of Ran in the nucleus or the cytoplasm. (b) and (c) Regulation of shuttling transport receptors by Ran. Nuclear import and export are mediated by shuttling receptors (R) which recognize and bind to nuclear localization sequences (NLS) or nuclear export sequences (NES), respectively. (b) An import substrate (S) bearing an NLS is bound by a β‐like receptor (R) in the cytoplasm. After translocation, the high levels of RanGTP in the nucleoplasm promote the dissociation of the complex by direct binding to the receptor. The receptor is recycled back to the cytoplasm. In the cytoplasm, RanGAP and RanBP1 promote GTP hydrolysis by Ran and thus the dissociation of RanGTP/receptor complexes. The receptor can then initiate another round of import. (c) The presence of high concentrations of RanGTP in the nucleus facilitates the binding of the export receptors (R) to the NES. In the cytoplasm, RanGAP and RanBP1 promote GTP hydrolysis by Ran and thus the release of the export substrate (S). The receptor enters the nucleus to initiate a new round of export.

The export pathways of uracyl‐rich (U snRNA) and (mRNAs). (a) CBC binds to the cap structure of U snRNAs and recruits other cellular factors (X). These factors are likely to provide a link between uracyl‐rich small nuclear ribonucleoproteins (U snRNPs) and the export receptor CRM1. In the cytoplasm, RanGAP and RanBP1 promote GTP hydrolysis by Ran and thus the dissociation of the CRM1 from the U snRNPs. (b) mRNAs are exported in association with proteins as large RNP complexes. RNA‐binding proteins bearing a nuclear export signal (NES) are defined as adaptors (A). The presence of high concentrations of RanGTP in the nucleus facilitates the binding of the export receptors (R) to the NES. Prior to translocation some (NR) factors are stripped from the RNA. In the cytoplasm, RanGAP and RanBP1 promote GTP hydrolysis by Ran and thus the dissociation of the receptor/RNP complexes.

Nucleoporins and nuclear pore‐associated proteins involved in RNA export are shown on this schematical representation of the three‐dimensional structure of the (NPC). Yeast nucleoporins are indicated in red while the vertebrate homologues are shown in black. CAN/Nup159, Nup88/Nup82, and Dbp5 are on the cytoplasmic side of the NPC. Gle2 and Mex67p have been localized at the pore but also in the cytoplasm and nucleoplasm. The localization of the yeast Nup84p complex is unknown. CC, central channel; CF, cytoplasmic filaments; CR, cytoplasmic ring; NR, nuclear ring; ONM, outer nuclear membrane; INM, inner nuclear membrane.

Localization of mRNAs in (a) Saccharomyces cerevisiae, (b) Drosophila melanogaster and (c) Xenopus laevis. (a) Localization of ASH1 mRNA in yeast during cell division (courtesy of R. Jansen). (b) Localization of bicoid (upper panel) and osk (lower panel) mRNAs to the anterior and posterior pole of the Drosophila oocyte, respectively (courtesy of D. St Johnston). (c) Localization of Vg1 mRNA to the vegetal hemisphere (left panel) and to the vegetal cortex (right panel) in a stage III and a stage V Xenopus oocyte, respectively (courtesy of Q. Zhang and J. Yisraeli). The images were obtained by in situ hybridization followed by confocal (a and c) or conventional microscopy (b).