A Ran-independent pathway for export of spliced mRNA

All major nuclear export pathways so far examined follow a general paradigm(1-3). Specifically, a complex is formed in the nucleus, containing the export cargo, a member of the importin-beta family of transporters and RanGTP, This complex is translocated across the nuclear pore to the cytoplasm, where hydrolysis of the GTP on Ran is stimulated by the GTPase-activating protein RanGAP(4,5). The activity of RanGAP is increased by RanBP1, which also promotes disassembly of RanGTP-cargo-transporter complexes(6,7). Here we investigate the role of RanGTP in the export of mRNAs generated by splicing. We show that nuclear injection of a Ran mutant (RanT24N)(8) or the normally cytoplasmic RanGAP potently inhibits the export of both tRNA and U1 snRNA(9), but not of spliced mRNAs. Moreover, nuclear injection of RanGAP together with RanBP1 blocks tRNA export but does not affect mRNA export, These and other data indicate that export of spliced mRNA is the first major cellular transport pathway that is independent of the export co-factor Ran.