Work

How the TREX-2 complex associates with the nuclear pore

Year: 2026

Type: article

Abstract: Nuclear pore complexes (NPCs) control nucleocytoplasmic transport in eukaryotes, yet their architecture remains incompletely understood. Here, we report a substantially extended structure of the human NPC, obtained by combining cryo-electron tomography, crosslinking mass spectrometry, and AI-assisted integrative modeling. We resolve the molecular arrangement of translocated promoter region (TPR), NUP153, NUP50, and ZC3HC1 and reveal that five additional proteins-TMEM209, SMPD4, GANP, Centrin-2, and ENY2-are incorporated into the NPC. Unexpectedly, GANP, Centrin-2, and ENY2, core members of the TREX-2 mRNA export complex, are built into the nuclear ring. This finding establishes TREX-2 not as a transiently associated factor, but as an integral NPC module, positioning it opposite of the cytoplasmic NUP214 mRNA export platform. Together, our results redefine the molecular composition of the inner ring, nuclear ring, and nuclear basket. They suggest a direct structural basis that couples TREX-2-mediated messenger ribonucleoprotein particle (mRNP) remodeling to NPC-facilitated transport.

Source: Molecular Cell

DOI: 10.1016/j.molcel.2026.10.006