In eukaryotic cells, the movement of macromolecules between the nucleus and cytoplasm is managed by the nucleocytoplasmic transport system. This system employs specialised receptors to ferry molecules through the nuclear pore complex (NPC), which functions as a selective barrier between these compartments. While the karyopherin family handles most macromolecule transport, mRNA export is specifically facilitated by the Nxf1-Nxt1 receptor, historically viewed as the sole pathway for bulk mRNA export. It has been proposed that the Transcription and Export complexes (TREX-1 and TREX-2) assist in this process by recruiting mRNAs during transcription and transferring them to the Nxf1-Nxt1 receptor.
Our studies, which combined genetic, biochemical, and single-molecule tracking techniques, have demonstrated that the TREX-2 complex can independently function as an mRNA export receptor. Remarkably, TREX-2 can transport mRNA directly to the cytoplasm, bypassing Nxf1-Nxt1. The TREX-2 complex includes an mRNA-binding "head" connected to a "base" anchored to the nucleoplasmic side of the NPC by an extended unstructured protein segment. This structure allows only the mRNA-bound "head" to cross into the cytoplasm while the "base" remains nuclear-bound.
This discovery reveals a unique mRNA transport mechanism through the NPC that does not depend on traditional shuttling proteins, challenging the established belief that Nxf1-Nxt1 is solely responsible for bulk mRNA export. Since nuclear mRNA export is crucial for gene expression and RNA quality control, our findings significantly advance the understanding of this essential cellular process.