Once the processing of an mRNA is completed in the nucleus, it remains associated with specific proteins in a messenger ribonuclear protein complex, or mRNP. The principal transporter of mRNPs out of the nucleus is the mRNP exporter, a heterodimeric protein composed of a large subunit called nuclear export factor 1 (NXF1) and a small subunit called nuclear export transporter 1 (NXT1). Multiple NXF1/NXT1 dimers bind to nuclear mRNPs through cooperative interactions with the RNA and other mRNP adapter proteins that associate with nascent pre-mRNAs during transcriptional elongation and pre-mRNA processing. In many respects, the subunits of NXF1/NXT1 act like a nuclear transport receptor that binds to an NLS or NES, since both subunits interact with the FG-repeats of FG-nucleoporins, and this interaction allows them to diffuse through the central channel of the NPC.

The process of mRNP export does not require Ran, and thus the unidirectional transport of mRNA out of the nucleus requires a source of energy other than GTP hydrolysis by Ran. Once the mRNP-NXF1/NXT1 complex reaches the cytoplasmic side of the NPC, NXF1 and NXT1 dissociate from the mRNP with the help of the RNA helicase Dbp5, which is associated with cytoplasmic NPC filaments. Recall that RNA helicases use the energy derived from hydrolysis of ATP to move along RNA molecules, separating double-stranded RNA chains and dissociating RNA-protein complexes (see Chapter 5). This leads to the simple idea that Dpb5, which is associated with the cytoplasmic side of the nuclear pore complex, acts as an ATP-driven motor to remove NXF1/NXT1 from the mRNP complexes as they emerge on the cytoplasmic side of the NPC. The assembly of NXF1/NXT1 onto mRNPs on the nucleoplasmic side of the NPC and the subsequent ATP-dependent removal of NXF1/NXT1 from mRNPs on the cytoplasmic side of the NPC creates a concentration gradient of mRNP-NXF1/NXT1, which drives unidirectional export. After being removed from the mRNP, the free NXF1 and NXT1 subunits that have been stripped from the mRNA by Dbp5 helicase are imported back into the nucleus by a process that depends on Ran and a nuclear transport receptor (Figure 13-37b).

In Ran-dependent nuclear export (discussed in the previous subsection), hydrolysis of GTP by Ran on the cytoplasmic side of the NPC causes dissociation of the nuclear transport receptor from its cargo. In basic outline, the Ran-independent nuclear export discussed here operates by a similar mechanism, except that Dbp5p on the cytosolic side of the NPC uses hydrolysis of ATP to dissociate the mRNP exporter from mRNA.