The NXT step in Tap-dependent mRNA export

Abstract

The majority of mRNAs exit the nucleus in association with a protein called Tap, which shuttles between the nucleus and the cytoplasm through its interaction with proteins of the nuclear pore complex (NPC). Tap forms a heterodimer with a protein called NXT1, but the role of NXT1 in mRNA export has been controversial. Two new papers now demonstrate that NXT1 enhances the association of Tap with the NPC and that this function is crucial for efficient Tap-mediated mRNA export [1xRNA export mediated by Tap involves NXT1-dependent interactions with the nuclear pore complex. Levesque, L. et al. J. Biol. Chem. 2001; 276: 44953–44962Crossref | PubMed | Scopus (36)See all References, 2xFormation of Tap/NXT1 heterodimers activates Tap-dependent nuclear mRNA export by enhancing recruitment to nuclear pore complexes. Wiegand, H.L. et al. Mol. Cell. Biol. 2002; 22: 245–256Crossref | Scopus (82)See all References].Using a mammalian two-hybrid assay, Cullen and coworkers found that overexpression of NXT1 caused a five-fold enhancement of the interaction between Tap and the nucleoporin CG1 [2xFormation of Tap/NXT1 heterodimers activates Tap-dependent nuclear mRNA export by enhancing recruitment to nuclear pore complexes. Wiegand, H.L. et al. Mol. Cell. Biol. 2002; 22: 245–256Crossref | Scopus (82)See all References][2]. Paschal and colleagues obtained similar results for the in vitro binding of Tap to two other nucleoporins, p62 and p58, in a microtiter-well binding assay [1xRNA export mediated by Tap involves NXT1-dependent interactions with the nuclear pore complex. Levesque, L. et al. J. Biol. Chem. 2001; 276: 44953–44962Crossref | PubMed | Scopus (36)See all References][1]. Both sets of authors observed a clear link between Tap–NXT1 interaction, NPC binding and efficient mRNA export by employing heterologous systems that uncouple the nuclear export activity of Tap from its ability to bind to mRNA [1xRNA export mediated by Tap involves NXT1-dependent interactions with the nuclear pore complex. Levesque, L. et al. J. Biol. Chem. 2001; 276: 44953–44962Crossref | PubMed | Scopus (36)See all References, 2xFormation of Tap/NXT1 heterodimers activates Tap-dependent nuclear mRNA export by enhancing recruitment to nuclear pore complexes. Wiegand, H.L. et al. Mol. Cell. Biol. 2002; 22: 245–256Crossref | Scopus (82)See all References].Furthermore, two sets of experiments reported by Wiegand et al. [2xFormation of Tap/NXT1 heterodimers activates Tap-dependent nuclear mRNA export by enhancing recruitment to nuclear pore complexes. Wiegand, H.L. et al. Mol. Cell. Biol. 2002; 22: 245–256Crossref | Scopus (82)See all References][2] elegantly demonstrated evolutionary conservation of the role of NXT1 in Tap-mediated mRNA export. First, the authors showed that inactivation of NXT1 in a Drosophila cell line by RNA interference caused nuclear accumulation of bulk poly(A)? RNA. They then found that the Caenorhabditis elegans Tap homolog, which fails to bind to human NXT1, could only mediate mRNA export in human cells when the worm NXT1 protein was coexpressed.Nuclear mRNA export by the yeast Tap homolog, Mex67p, requires its association with the cofactor Mtr2p. Although Mtr2p and NXT1 do not exhibit sequence similarity, the demonstration of a central role for NXT1 in Tap-mediated mRNA export resolves a previously curious discrepancy between the mammalian and yeast mRNA systems. Future studies will undoubtedly focus on determining whether the Tap–NXT1 interaction bears regulatory significance, perhaps by targeting mRNA export complexes to sites of increasing binding affinity within the NPC or by involvement in mRNA release on the cytoplasmic side of the pore.