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TitleStructural basis for the synergistic assembly of the snRNA export complex.
Journal, issue, pagesNat Struct Mol Biol, Vol. 32, Issue 8, Page 1555-1566, Year 2025
Publish dateJul 3, 2025
AuthorsEtienne Dubiez / William Garland / Maja Finderup Brask / Elisabetta Boeri Erba / Torben Heick Jensen / Jan Kadlec / Stephen Cusack /
PubMed AbstractThe 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. ...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.
External linksNat Struct Mol Biol / PubMed:40610714 / PubMed Central
MethodsEM (single particle)
Resolution2.62 Å
Structure data

EMDB-52115, PDB-9hfl:
Cryo-EM structure of the human snRNA export complex comprising CBC-PHAX-CRM1-RanGTP and capped-RNA
Method: EM (single particle) / Resolution: 2.62 Å

Chemicals

ChemComp-GTP:
GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying molecule*YM

ChemComp-MG:
Unknown entry

ChemComp-GTA:
P1-7-METHYLGUANOSINE-P3-ADENOSINE-5',5'-TRIPHOSPHATE

ChemComp-HOH:
WATER

Source
  • homo sapiens (human)
KeywordsRNA BINDING PROTEIN / snRNA export / Exportin / Cap-binding / Co-transcriptional regulation

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