The world is an ever-changing environment. The cell's ability to adapt to environmental changes and take advantage of new resources is crucial to its survival. Gene expression lies at the heart of this process. Upon extracellular or intracellular cues, the cell transcribes mRNAs needed to generate proteins that will carry out a given response. These mRNAs have to traverse then nuclear envelope through the NPC to reach sites of translation in the cytoplasm. This process is known as mRNA export and is mediated by NPC components and soluble transport receptors. Regulation of mRNA export has been demonstrated for stress conditions such as heat-shock, low temperature, and ethanol stress (1) (3), and specialized export pathways have been found for specific endogenous and viral mRNAs (2) (4).
We are interested in the transport of macromolecules through the NPC. By comparing the mRNA export pathway mediated by the receptors Mex67-Mtr2 (TAP-p15 in metazoans) and the protein transport pathway mediated by karyopherins (Kaps), we observe that striking parallel control mechanisms spatially dictate transport factor activities. At the NPC cytoplasmic face, the Kap pathway requires RanGAP (Ran GTPase-activating protein) for stimulating the activity of the small GTPase Ran (5), and the mRNA export pathway requires Gle1 and inositol hexakisphosphate (IP6) cofactors for stimulating the ATPase activity of the DEAD-box protein Dbp5. Thus, an NTPase activating protein is critical for both transport events. In addition, juxtaposition of the respective proteins is mediated by specific Nup binding sites and enhanced by potentially regulatory factors (SUMO modification and IP6, respectively).
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3. C. Saavedra et al. Genes Dev. 10, 1608 (1996).
4. M. Bray et al. Proc. Natl. Acad. Sci. USA 91, 1256 (1994).
5. H. Fried and U. Kutay. Cell. Mol. Life Sci. 60, 1659 (2003).
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