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PreprintCited by 94Nuclear Structure and FunctionProtein Structure and DynamicsRNA Research and Splicing

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The Molecular Architecture of the Nuclear Basket

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Singh, Digvijay, Soni, Neelesh, Hutchings, Joshua, Echeverria, Ignacia, Shaikh, Farhaz, Duquette, Madeleine, Suslov, Sergey, Li, Zhixun, van Eeuwen, Trevor, Molloy, Kelly, Shi, Yi, Wang, Junjie, Guo, Qiang, Chait, Brian T., Fernandez-Martinez, Javier, Rout, Michael P., Sali, Andrej, Villa, Elizabeth·2024·Cell
DOI 10.1101/2024.03.27.587068PMC PMC11416316

Preprint — published as 10.1016/j.cell.2024.07.020

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Abstract

The nuclear pore complex (NPC) is the sole mediator of nucle-ocytoplasmic transport. Despite great advances in understanding its conserved core architecture, the peripheral regions can exhibit considerable variation within and between species. One such structure is the cage-like nuclear basket. Despite its crucial roles in mRNA surveillance and chromatin organization, an architectural understanding has remained elusive. Using in-cell cryo-electron tomography and subtomogram analysis, we explored the NPC’s structural variations and the nuclear basket across fungi (yeast; S. cerevisiae ), mammals (mouse; M. musculus ), and protozoa ( T. gondii ). Using integrative structural modeling, we computed a model of the basket in yeast and mammals that revealed how a hub of Nups in the nuclear ring binds to basket-forming Mlp/Tpr proteins: the coiled-coil domains of Mlp/Tpr form the struts of the basket, while their unstructured termini constitute the basket distal densities, which potentially serve as a docking site for mRNA preprocessing before nucleocytoplasmic transport

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Metadata

Authors
Singh, D., Soni, N., Hutchings, J., Echeverria, I., Shaikh, F., Duquette, M., Suslov, S., Li, Z., van Eeuwen, T., Molloy, K., Shi, Y., Wang, J., Guo, Q., Chait, B. T., Fernandez-Martinez, J., Rout, M. P., Sali, A., & Villa, E.
Affiliations
  • University of California San Diego (US)
  • University of California, San Francisco (US)
  • Peking University (CN)
  • Rockefeller University (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
  • Rout, Michael P.
  • Villa, Elizabeth
ORCID
Venue
Cell
Publisher
openRxiv
Published
2024-03-28
Volume
187
Issue
19
Pages
5267-5281.e13
ISSN
0092-8674 (ISSN-L)
DOI
10.1101/2024.03.27.587068
PMC
PMC11416316
OpenAlex
W4401459440
Cited by
94
References
1
Citations by year
2026: 36 · 2025: 47 · 2024: 11
FWCI
12.80
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Cell (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
Funders
  • National Science Foundation (1818129, 1920374)
  • Howard Hughes Medical Institute
  • Damon Runyon Cancer Research Foundation (DRG-2364-19)
  • European Molecular Biology Organization (ALTF 871-2020)
  • Agouron Institute
  • National Institutes of Health (NSF-1818129, GM109824)
  • University of California, San Diego
  • National Institute on Aging (K99AG080112)
  • National Institute of General Medical Sciences (R01GM083960, P41GM109824, R01GM117212, R35GM137905, R01GM112108, T32GM133351, R01GM129245)
  • National Institute of Allergy and Infectious Diseases (U54AI170856)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords
nuclear basket, nuclear pore complex, nuclear transport, nucleoporins, coiled-coil domain, mRNA surveillance, nuclear rings, integrative structural modeling, Saccharomyces cerevisiae, Mus musculus, Toxoplasma gondii

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