Two closely related human nuclear export factors utilize entirely distinct export pathways.
Nuclear mRNA export mediated by the human protein TAP requires a carboxy-terminal domain that directly interacts with components of the nuclear pore complex. Here we demonstrate that NXF3, a human RNA binding protein related to TAP, lacks this domain yet retains the ability to export tethered RNA transcripts and to shuttle between the nucleus and the cytoplasm. NXF3 contains a novel Crm1-dependent nuclear export signal that compensates in cis for the loss of the nuclear pore targeting domain. NXF3-dependent RNA export is therefore blocked by Crm1-specific inhibitors that do not affect TAP function. Thus, while the related TAP and NXF3 proteins are both capable of mediating nuclear RNA export, they do so via unrelated export pathways.
Yang
J
J
Howard Hughes Medical Institute, Department of Genetics, Duke University Medical Center, Durham, NC 27710, USA.
Bogerd
H P
HP
Wang
P J
PJ
Page
D C
DC
Cullen
B R
BR
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D015151:Immunoblotting; D028884:Karyopherins; D008958:Models, Molecular; D029543:Nucleocytoplasmic Transport Proteins; D011485:Protein Binding; D021382:Protein Sorting Signals / Q000502:physiology; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D020798:Two-Hybrid System Techniques; D000097606:Exportin 1 Protein
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D002352:Carrier Proteins; D028884:Karyopherins; D029543:Nucleocytoplasmic Transport Proteins; D021382:Protein Sorting Signals; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D000097606:Exportin 1 Protein; C436949:NXF3 protein, human; C073119:TAP1 protein, human