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Cited by 9RNA Research and SplicingNuclear Structure and FunctionGenomics and Chromatin Dynamics

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Structural basis for the synergistic assembly of the snRNA export complex

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Dubiez, Etienne, Garland, William, Finderup Brask, Maja, Boeri Erba, Elisabetta, Heick Jensen, Torben, Kadlec, Jan, Cusack, Stephen·2025·Nature Structural & Molecular Biology
DOI 10.1038/s41594-025-01595-5PMC PMC12350170

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Abstract

The nuclear cap-binding complex (CBC) and its partner Arsenite-Resistance Protein 2 (ARS2) regulate the fate of RNA polymerase II transcripts via mutually exclusive interactions with RNA effectors. One such effector is PHAX, which mediates the nuclear export of U-rich small nuclear RNAs (snRNAs). Here we present the cryo-electron microscopy structure of the human snRNA export complex comprising phosphorylated PHAX, CBC, CRM1–RanGTP and capped RNA. The central region of PHAX bridges CBC to the export factor CRM1–RanGTP, while also reinforcing cap dinucleotide binding. Additionally, PHAX interacts with a distant region of CRM1, facilitating contacts of the essential phosphorylated region of PHAX with the prominent basic surface of RanGTP. CBC engagement within the snRNA export complex is incompatible with its binding to other RNA effectors such as ALYREF or NCBP3. We demonstrate that snRNA export complex formation requires synergistic binding of all its components, which in turn displaces ARS2 from CBC and commits the complex for export.

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Metadata

Authors
Dubiez, E., Garland, W., Finderup Brask, M., Boeri Erba, E., Heick Jensen, T., Kadlec, J., & Cusack, S.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • Aarhus University (DK)
  • European Molecular Biology Laboratory (FR)
Corresponding author
  • Kadlec, Jan
  • Cusack, Stephen
ORCID
Venue
Nature Structural & Molecular Biology
Publisher
Springer Science and Business Media LLC
Published
2025-07-03
Volume
32
Issue
8
Pages
1555-1566
ISSN
  • 1545-9985 (ISSN-L)
  • 1545-9993
DOI
10.1038/s41594-025-01595-5
PMC
PMC12350170
OpenAlex
W4412008164
Cited by
9
References
2
Citations by year
2026: 7 · 2025: 2
FWCI
2.69
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Structural & Molecular Biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
Funders
  • European Molecular Biology Laboratory (UAR 3518 CNRS-CEA-UGA-EMBL)
  • Agence Nationale de la Recherche (UAR 3518 CNRS-CEA-UGA-EMBL, ANR-24-CE11-4977, ANR-17-EURE-0003, ANR-17-EURE-, ANR-21-CE11-0021, ANR-17, ANR-10, ANR-10-INBS-0005)
  • Novo Nordisk
  • Centre National de la Recherche Scientifique (ANR‐17‐EURE‐0003, UAR 3518 CNRS-CEA-UGA-EMBL)
  • French Infrastructure for Integrated Structural Biology (UAR 3518 CNRS-CEA-UGA-EMBL, ANR-17-EURE-0003, ANR-10-INBS-0005, ANR-10-INBS-000502, ANR-10-INBS)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
nuclear cap-binding complex, ARS2, small nuclear RNA, RNA export, RNA-protein interactions, RNA polymerase II transcripts, ALYREF, protein complex structure
MeSH terms
Exportin 1 Protein, Humans, Models, Molecular, Nuclear Proteins, Phosphoproteins, Phosphorylation, Protein Binding, RNA, Small Nuclear, RNA-Binding Proteins, Receptors, Cytoplasmic and Nuclear, Cryoelectron Microscopy, ran GTP-Binding Protein, Active Transport, Cell Nucleus, Karyopherins, Nucleocytoplasmic Transport Proteins, Nuclear Cap-Binding Protein Complex

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