MCB
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wiegand, H. L.
Right arrow Articles by Cullen, B. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wiegand, H. L.
Right arrow Articles by Cullen, B. R.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, January 2002, p. 245-256, Vol. 22, No. 1
0270-7306/01/$04.00+0     DOI: 10.1128/MCB.22.1.245-256.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Formation of Tap/NXT1 Heterodimers Activates Tap-Dependent Nuclear mRNA Export by Enhancing Recruitment to Nuclear Pore Complexes

Heather L. Wiegand, Glen A. Coburn, Yan Zeng, Yibin Kang,,{dagger} Hal P. Bogerd, and Bryan R. Cullen*

Howard Hughes Medical Institute and Department of Genetics, Duke University Medical Center, Durham, North Carolina 27710

Received 6 July 2001/ Returned for modification 15 August 2001/ Accepted 28 September 2001

The Tap protein has been shown to activate the nuclear export of mRNA species bearing retroviral constitutive transport elements and is also believed to play an essential role in the sequence nonspecific export of cellular mRNAs. However, it has remained unclear how Tap activity is regulated in vivo. Here, we report that the small NXT1/p15-1 protein functions as a critical cofactor for Tap-mediated mRNA export in both human and invertebrate cells. In the absence of NXT1 binding, the Tap protein is unable to effectively interact with components of the nuclear pore complex and both Tap nucleocytoplasmic shuttling and the nuclear export of mRNA molecules tethered to Tap are therefore severely attenuated. Formation of a Tap/NXT1 heterodimer enhances nucleoporin binding both in vitro and in vivo and induces the formation of a Tap/NXT1/nucleoporin ternary complex that is likely to be a key intermediate in the process of nuclear mRNA export. The critical importance of NXT1 for the nuclear export of poly(A)+ RNA is emphasized by the finding that specific inhibition of the expression of the Drosophila homolog of human NXT1, by using RNA interference, results in the nuclear accumulation of poly(A)+ RNA in cultured insect cells. These data suggest that NXT1 may act as a molecular switch that regulates the ability of Tap to mediate nuclear mRNA export by controlling the interaction of Tap with components of the nuclear pore.

* Corresponding author. Mailing address: Howard Hughes Medical Institute, Box 3025, Duke University Medical Center, Durham, NC 27710. Phone (919) 684-3369. Fax: (919) 681-8979. E-mail: culle002{at}mc.duke.edu.

{dagger} Present address: Department of Cell Biology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.

Molecular and Cellular Biology, January 2002, p. 245-256, Vol. 22, No. 1
0022-538X/01/$04.00+0     DOI: 10.1128/MCB.22.1.245-256.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 2002 by the American Society for Microbiology. All rights reserved.