Functions of the GTPase Ran in RNA export from the nucleus

Abstract

Significant and exciting advances in the field of RNA and protein export have been made recently, due in large part to discovery of the roles played by Ran, a small, soluble GTPase present in both the nucleus and cytoplasm of all eukaryotic cells. Ran is thought to be primarily bound to GTP in the nucleus and to GDP in the cytoplasm, as a result of the assymetric distribution of factors that interact with Ran to promote guanine nucleotide exchange (in the nucleus) and GTP hydrolysis (in the cytoplasm). A key function of the nuclear Ran.GTP is to support formation of complexes containing an export receptor (an exportin) and cargos such as RNAs, RNPs or proteins that are destined for export. In the cytoplasm, removal of the Ran.GTP from the complex results in its destabilization and release of the export cargo. Although Ran.GTP is required for formation of the export complex, GTP hydrolysis does not appear to be necessary for translocation through the nuclear pore complex or cytoplasmic release. Nevertheless, the GTPase of Ran does appear to be required in as yet unidentified intranuclear steps prior to export of some, but not all, RNAs.