An ATP-gated molecular switch orchestrates human mRNA export

The nuclear export of mRNA is an important step in eukaryotic gene expression<sup>1</sup>. Despite recent molecular insights into how newly transcribed mRNAs are packaged into ribonucleoprotein complexes (mRNPs)<sup>2,3</sup>, 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.

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Publication Details

Journal
Nature
Published
2025-11-06
DOI
https://doi.org/10.1038/s41586-025-09832-z
Citations
6
Primary Topic
RNA Research and Splicing
Type
article
Field-Weighted Citation Impact
4.84
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article

An ATP-gated molecular switch orchestrates human mRNA export

Clemens Plaschka, Daria Riabov-Bassat, Thomas Pühringer, Dominik Handler et al.
6 citations
Nature
RNA Research and Splicing
4.84
article

An ATP-gated molecular switch orchestrates human mRNA export

Clemens Plaschka, Daria Riabov-Bassat, Thomas Pühringer, Dominik Handler, Belén Pacheco-Fiallos, Laura Fin, Julius Brennecke, Alexander William Phillips, Elisabeth Roitinger, Ulla Schellhaas, Ulrich Hohmann, Michael Szalay, László Tirián, Max Graf, Rupert Faraway
article en
6 citations

Abstract

The nuclear export of mRNA is an important step in eukaryotic gene expression<sup>1</sup>. Despite recent molecular insights into how newly transcribed mRNAs are packaged into ribonucleoprotein complexes (mRNPs)<sup>2,3</sup>, 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.

NatureVol. 649(8098)
Institute of Molecular Biotechnology (AT), University of Vienna (AT), Austrian Academy of Sciences (AT), Research Institute of Molecular Pathology (AT), Max Perutz Labs (AT), Vienna Biocenter (AT), Institute of Molecular Biology (DE), Medical University of Vienna (AT)
Openalex Percentile: Top 5%
RNA Research and Splicing
4.84
DOIOpen Access PDFOpenAlex
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