Structural basis for the synergistic assembly of the snRNA export complex

Etienne Dubiez; William Garland; Maja Finderup Brask; Elisabetta Boeri Erba; Torben Heick Jensen; Jan Kadlec; Stephen Cusack

doi:10.1038/s41594-025-01595-5

Structural basis for the synergistic assembly of the snRNA export complex

Etienne Dubiez
, William Garland
, Maja Finderup Brask
, Elisabetta Boeri Erba
, Torben Heick Jensen
, Jan Kadlec^*
, Stephen Cusack^*

^*Corresponding author for this work

Department of Molecular Biology and Genetics - RNA Biology and Innovation

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

2 Citations (Scopus)

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.

Original language	English
Journal	Nature Structural and Molecular Biology
Volume	32
Issue	8
Pages (from-to)	1555-1566
Number of pages	12
ISSN	1545-9993
DOIs	https://doi.org/10.1038/s41594-025-01595-5
Publication status	Published - Aug 2025

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@article{d819a83a15fd4474a1ad1284287b61b9,

title = "Structural basis for the synergistic assembly of the snRNA export complex",

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.",

author = "Etienne Dubiez and William Garland and \{Finderup Brask\}, Maja and \{Boeri Erba\}, Elisabetta and \{Heick Jensen\}, Torben and Jan Kadlec and Stephen Cusack",

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month = aug,

doi = "10.1038/s41594-025-01595-5",

language = "English",

volume = "32",

pages = "1555--1566",

journal = "Nature Structural and Molecular Biology",

issn = "1545-9993",

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Structural basis for the synergistic assembly of the snRNA export complex. / Dubiez, Etienne; Garland, William ; Finderup Brask, Maja et al.
In: Nature Structural and Molecular Biology, Vol. 32, No. 8, 08.2025, p. 1555-1566.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Structural basis for the synergistic assembly of the snRNA export complex

AU - Dubiez, Etienne

AU - Garland, William

AU - Finderup Brask, Maja

AU - Boeri Erba, Elisabetta

AU - Heick Jensen, Torben

AU - Kadlec, Jan

AU - Cusack, Stephen

PY - 2025/8

Y1 - 2025/8

N2 - 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.

AB - 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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DO - 10.1038/s41594-025-01595-5

M3 - Journal article

C2 - 40610714

AN - SCOPUS:105009617356

SN - 1545-9993

VL - 32

SP - 1555

EP - 1566

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

IS - 8

ER -

Structural basis for the synergistic assembly of the snRNA export complex

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