The nuclear pore complex (NPC) forms a selective permeability barrier between the nucleus and cytoplasm and mediates the transport of macromolecules between these two compartments. While the nucleo-cytoplasmic transport of most macromolecules is mediated by the karyopherin family of transport receptors, the export of mRNAs uses a unique, non-karyopherin-mediated pathway by Nxf1-Nxt1 in humans and Mex67-Mtr2 in yeast, which is the only known mRNA export receptor and is evolutionarily conserved from yeast to humans. Current models suggest that the TRanscription and EXport complex 1 and 2 (TREX-1 and TREX-2) are recruited to mRNAs during transcription elongation and deliver these to the transport receptor Mex67-Mtr2/Nxf1-Nxt1 that ultimately carries the mRNA cargo through the nucleopore channel. Intriguingly, Mex67 and Mtr2 are not essential genes in Schizosaccharomyces pombe (S. pombe), indicating that other mRNA export receptor(s) must exist.
Here we show that the evolutionarily conserved TREX-2 complex is a bona fide mRNA export receptor that can transport mRNAs through the nucleopore channel. While the TREX-2 complex is stably anchored to the nucleoplasmic side of the NPC through the extended C-terminal domain of the Sac3 subunit (GANP in humans), the FG-like repeat containing N-terminal part can enter the nuclear pore channel. We used biochemical and pair-correlation function (pCF) assays to show that the N-terminal part of Sac3 and the Pci2 subunit of the complex can be detected at the cytoplasmic side of the NPC. These results indicate that the RNA-binding part of the TREX-2 complex can pass through the FG-repeat phase of the NPC and reach the cytoplasm, while the extended C-terminal part of the complex remains anchored to the nuclear side of the NPC.
Overall, our results strongly suggest that the evolutionarily conserved TREX-2 complex serves as an mRNA-specific export receptor that can deliver mRNA cargo from the nucleus to the cytoplasm.