8R7L

Cryo-EM structure of the human TREX complex

Summary for 8R7L

• Entry DOI: 10.2210/pdb8r7l/pdb
• EMDB information: 18979
• Descriptor: Spliceosome RNA helicase DDX39B, THO complex subunit 1, THO complex subunit 2, ... (5 entities in total)
• Functional Keywords: mrna export, gene regulation
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 365947.37

Authors

Hohmann, U.,Pacheco-Fiallos, B.,Plaschka, C. (deposition date: 2023-11-25, release date: 2025-06-11, Last modification date: 2025-11-26)

Primary citation

Hohmann, U.,Graf, M.,Tirian, L.,Pacheco-Fiallos, B.,Schellhaas, U.,Fin, L.,Handler, D.,Philipps, A.W.,Riabov-Bassat, D.,Faraway, R.W.,Puhringer, T.,Szalay, M.F.,Roitinger, E.,Brennecke, J.,Plaschka, C.
An ATP-gated molecular switch orchestrates human messenger RNA export.
Nature, 2025

PubMed Abstract: The nuclear export of mRNA is an important step in eukaryotic gene expression. Despite recent molecular insights into how newly transcribed mRNAs are packaged into ribonucleoprotein complexes (mRNPs), the subsequent events that govern mRNA export are poorly understood. Here we uncover the molecular basis underlying key events of human mRNA export, including the remodelling of mRNP-bound transcription-export complexes (TREX), the formation of export-competent mRNPs, the docking of mRNPs at the nuclear pore complex (NPC), and the release of mRNPs at the NPC to initiate their export. Our biochemical and structural data show that the ATPase UAP56 (also known as DDX39) acts as a central molecular switch that directs nucleoplasmic mRNPs from TREX to NPC-anchored TREX-2 complexes through its ATP-gated mRNA-binding cycle. Collectively, these findings establish a mechanistic framework for a general and evolutionarily conserved mRNA export pathway.

PubMed: 41198879
DOI: 10.1038/s41586-025-09832-z

Experimental method

ELECTRON MICROSCOPY (4.12 Å)