TAP binds to the constitutive transport element (CTE) through a novel RNA-binding motif that is sufficient to promote CTE-dependent RNA export from the nucleus.
The constitutive transport element (CTE) of the simian type D retroviruses overcomes nuclear retention and allows nuclear export of unspliced viral RNAs by recruiting TAP, a host factor which is thought to be required for export of cellular mRNAs. In this report, we show that the first 372 amino acid residues of TAP, comprising a stretch of leucine-rich repeats, are both necessary and sufficient for binding to the CTE RNA and promoting its export to the cytoplasm. Moreover, like the full-length protein, this domain migrates to the cytoplasm upon nuclear co-injection with the CTE RNA. Together, these results indicate that the CTE-binding domain includes the signals for nuclear export. We also describe a derivative of TAP that bears a triple amino acid substitution within the CTE-binding domain and substantially reduces the export of mRNAs from the nucleus. This provides further evidence for a role for TAP in this process. Thus, the CTE-binding domain of TAP defines a novel RNA-binding motif which has dual functions, both recognizing the CTE RNA and interacting with other components of the nuclear transport machinery.
Braun
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IC
University of Geneva, Department of Molecular Biology, 30 quai Ernest-Ansermet, 1211 Geneva 4, Switzerland.
Rohrbach
E
E
Schmitt
C
C
Izaurralde
E
E
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D001693:Biological Transport, Active; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D021382:Protein Sorting Signals / Q000235:genetics; D017433:Protein Structure, Secondary; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014982:Xenopus laevis
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D021382:Protein Sorting Signals; D012333:RNA, Messenger; D011994:Recombinant Proteins; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; C486172:Tap1 protein, rat