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TitleAn ATP-gated molecular switch orchestrates human mRNA export.
Journal, issue, pagesNature, Vol. 649, Issue 8098, Page 1042-1050, Year 2026
Publish dateNov 6, 2025
AuthorsUlrich Hohmann / Max Graf / László Tirián / Belén Pacheco-Fiallos / Ulla Schellhaas / Laura Fin / Dominik Handler / Alexander W Phillips / Daria Riabov-Bassat / Rupert Faraway / Thomas Pühringer / Michael-Florian Szalay / Elisabeth Roitinger / Julius Brennecke / Clemens Plaschka /
PubMed AbstractThe 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 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.
External linksNature / PubMed:41198879 / PubMed Central
MethodsEM (single particle)
Resolution3.5 - 5.89 Å
Structure data

18977

8r7j

EMDB-18977, PDB-8r7j:
Cryo-EM structure of the human TREX-2 complex
Method: EM (single particle) / Resolution: 3.5 Å

18978

8r7k

EMDB-18978, PDB-8r7k:
Cryo-EM structure of the human UAP56 - TREX-2 complex
Method: EM (single particle) / Resolution: 3.5 Å

18979

8r7l

EMDB-18979, PDB-8r7l:
Cryo-EM structure of the human TREX complex
Method: EM (single particle) / Resolution: 4.12 Å

EMDB-18980: Structure of a human TREX complex (with the THO tetramer).
Method: EM (single particle) / Resolution: 5.89 Å

EMDB-18981: Structure of the human UAP56 RecA1 RecA2 - TREX-2 complex
Method: EM (single particle) / Resolution: 4.22 Å

Chemicals

ChemComp-ANP:
PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / AMP-PNP, energy-carrying molecule analogue*YM

Source
  • homo sapiens (human)
KeywordsGENE REGULATION / mRNA export / nuclear pore basket

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