Nucleocytoplasmic Transport: Integrating mRNA Production and Turnover with Export through the Nuclear Pore

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Abstract
Separation of the nucleus and cytoplasm, maintained by two membrane bilayers that form the nuclear envelope, allows for spatial control over transcription factors and signaling mole- cules. This compartmentalization further ensures the presence of specialized environments for different stages of gene expres- sion, such as transcription and protein production. Selective exchange between these two compartments is clearly impor- tant as well. Whereas many types of active transport between the nucleus and cytoplasm rely on transport receptors in the importin- superfamily, export of mRNA utilizes distinct sol- uble machinery (6, 92). Moreover, in general mRNA export does not depend on a specific motif in the cargo, as has been demonstrated in many other cases of receptor-cargo interac- tions (22). Recent progress in identifying soluble factors im- portant to mRNA trafficking is beginning to reveal the molec- ular basis for functional coupling between steps in mRNA biogenesis and how such coupling, rather than a consensus motif, brings specificity to mRNA export. Studies with Saccharomyces cerevisiae revealed that the key modulators of cellular mRNA export are unrelated to canon- ical importin--related receptors. Specifically, yeast deficient in a gene called MEX67 accumulate poly(A) RNA in the nucleus (73). A second protein, Mtr2p, binds Mex67p, and this interaction is required for the export of poly(A) RNA in yeast (71, 77). In an independent avenue of investigation, involving metazoan cells and the simian type D retrovirus Mason Pfizer monkey virus, the cellular protein TAP was found to facilitate export of RNA containing the viral constitutive transport ele- ment (CTE) (8, 32). TAP, confirmed to be the human ortho- logue of Mex67p, has been redesignated NXF1 (nuclear export factor 1).