In eukaryotic cells, the exchange of macromolecules between the nucleus and cytoplasm is orchestrated by the nucleocytoplasmic transport system. This system uses specialised receptors to guide molecules through the nuclear pore complex (NPC), which acts as a selective barrier. While the karyopherin family mediates the majority of macromolecular transport, mRNA export has been primarily attributed to the Nxf1-Nxt1 receptor, traditionally viewed as the sole conduit for bulk mRNA export. The Transcription and Export complexes (TREX-1 and TREX-2) are thought to assist by recruiting mRNAs during transcription and delivering them to Nxf1-Nxt1.
Our study, integrating genetic, biochemical, and single-molecule imaging approaches, demonstrates that the TREX-2 complex can independently mediate mRNA export. Strikingly, TREX-2 facilitates direct mRNA transport to the cytoplasm without relying on Nxf1-Nxt1. The complex consists of an mRNA-binding "head" domain connected to a "base" that anchors to the nucleoplasmic side of the NPC via an extended, unstructured region. This configuration allows the "head" to translocate into the cytoplasm while the "base" remains nuclear-bound.
These findings uncover an alternative mRNA export mechanism that operates independently of canonical shuttling receptors, challenging the prevailing model of bulk mRNA export. Given the central role of nuclear export in gene expression and RNA surveillance, our study provides critical new insights into the diversity and complexity of RNA trafficking pathways.