Nuclear transporters exportins

Because the export machinery selectively binds transport-competent mRNPs, i.e., mRNAs associated with the appropriate nuclear proteins, the diffusion-based model for intranuclear RNA movement provides an additional checkpoint for gene expression at the level of mRNA export. This type of control has been demonstrated for tRNA export only mature tRNAs are transported to the cytoplasm because incompletely processed tRNAs do not efficiently bind to exportin-t, the tRNA-specific export receptor. 

Fig. 3 The microRNA (miRNA) pathway. An miRNA is first transcribed as part of an imperfect hairpin in a longer Pol II transcript with 5 cap (open circle) and polyadenosine tail (AAAAAA). The hairpin (pre-miRNA) is removed from the transcript by the nuclear RNase III type enzyme Drosha and its partner, DGCR8. Exportin-5 (Xpo-5) transports the resulting by-product to the cytoplasm, where Dicer liberates a short-lived miRNA duplex. The duplex is unwound, and one strand enters RISC. If the miRNA is mismatched to its target (left), it does not induce cleavage, but may inhibit translation. With a perfect or near-perfect match (right), the target RNA is destroyed by RISC.

Exportins Transport Proteins Containing Nuclear-Export Signals out of the Nucleus... 

Studies with HIV mutants showed that transport of unspllced 9-kb and singly spliced 4-kb viral mRNAs from the nucleus to the cytoplasm requires the virus-encoded Rev protein. Subsequent biochemical experiments demonstrated that Rev binds to a specific Rev-response element (RRE) present In HIV RNA. In cells infected with HIV mutants lacking the RRE, unspllced and singly spliced viral mRNAs remain in the nucleus, demonstrating that the RRE is required for Rev-mediated stimulation of transport. Rev contains a leucine-rich NES that Interacts with exportin 1 complexed with Ran GTP. As a result. Rev exports unspllced and singly spliced HIV mRNAs through interactions with exportin I and the nuclear pore complex. 

After pre-tRNAs are processed In the nucleoplasm, the mature tRNAs are transported to the cytoplasm through nuclear pore complexes by exportin-t, as discussed previously. In the cytoplasm, tRNAs are passed between aminoacyl-tRNA synthetases, elongation factors, and ribosomes during protein synthesis (Chapter 4). Thus tRNAs generally are associated with proteins and spend little time free in the cell, as Is also the case for mRNAs and rRNAs. 

RNAs are transported from the nucleus to the cytoplasm as ribonucleoproteins, which are targeted for export by a specific amino acid sequence called the nuclear export signal. The nucleoprotein forms a complex with additional proteins called exportins and with Ran. This complex is transported through the pore to the cytoplasm, where RanGAP activates hydrolysis of the bound GTP. In the absence of GTP, the complex dissociates with the release of RNA into the cytoplasm, and the exportins and Ran are transported back to the nucleus. 

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