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Molecular and Cellular Biology, August 2002, p. 5405-5418, Vol. 22, No. 15
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.15.5405-5418.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Nuclear Export of mRNA by TAP/NXF1 Requires Two Nucleoporin-Binding Sites but Not p15

Isabelle C. Braun, Andrea Herold, Michaela Rode, and Elisa Izaurralde*

European Molecular Biology Laboratory, D-69117 Heidelberg, Germany

Received 16 January 2002/ Returned for modification 27 February 2002/ Accepted 23 April 2002

Metazoan NXF1/p15 heterodimers promote export of bulk mRNA through nuclear pore complexes (NPC). NXF1 interacts with the NPC via two distinct structural domains, the UBA-like domain and the NTF2-like scaffold, which results from the heterodimerization of the NTF2-like domain of NXF1 with p15. Both domains feature a single nucleoporin-binding site, and they act synergistically to promote NPC translocation. Whether the NTF2-like scaffold (and thereby p15) contributes only to NXF1/NPC association or is also required for other functions, e.g., to impart directionality to the export process by regulating NXF1/NPC or NXF1/cargo interactions, remains unresolved. Here we show that a minimum of two nucleoporin-binding sites is required for NXF1-mediated export of cellular mRNA. These binding sites can be provided by an NTF2-like scaffold followed by a UBA-like domain (as in the wild-type protein) or by two NTF2-like scaffolds or two UBA-like domains in tandem. In the latter case, the export activity of NXF1 is independent of p15. Thus, as for the UBA-like domain, the function of the NTF2-like scaffold is confined to nucleoporin binding. More importantly, two copies of either of these domains are sufficient to promote directional transport of mRNA cargoes across the NPC.


* Corresponding author. Mailing address: European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany. Phone: 49 6221 387 389. Fax: 49 6221 387 518. E-mail: izaurralde{at}embl-heidelberg.de.


Molecular and Cellular Biology, August 2002, p. 5405-5418, Vol. 22, No. 15
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.15.5405-5418.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




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