Two closely related human nuclear export factors utilize entirely distinctexport pathways

Nuclear mRNA export mediated by the human protein TAP requires a carboxy-te rminal domain that directly interacts with components of the nuclear pore c omplex. Here we demonstrate that NXF3, a human RNA binding protein related to TAP, lacks this domain yet retains the ability to export tethered RNA tr anscripts and to shuttle between the nucleus and the cytoplasm. NXF3 contai ns a novel Crm1-dependent nuclear export signal that compensates in cis for the loss of the nuclear pore targeting domain. NXF3-dependent RNA export i s therefore blocked by Crm1 -specific inhibitors that do not affect TAP fun ction. Thus, while the related TAP and NXF3 proteins are both capable of me diating nuclear RNA export, they do so via unrelated export pathways.