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Cited by 65RNA and protein synthesis mechanismsNuclear Structure and FunctionRNA Research and Splicing

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Principles of human pre-60 S biogenesis

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Vanden Broeck, Arnaud, Klinge, Sebastian·2023·Science
DOI 10.1126/science.adh3892PMC PMC10054963

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Abstract

During the early stages of human large ribosomal subunit (60 S ) biogenesis, an ensemble of assembly factors establishes and fine-tunes the essential RNA functional centers of pre-60 S particles by an unknown mechanism. Here, we report a series of cryo–electron microscopy structures of human nucleolar and nuclear pre-60 S assembly intermediates at resolutions of 2.5 to 3.2 angstroms. These structures show how protein interaction hubs tether assembly factor complexes to nucleolar particles and how guanosine triphosphatases and adenosine triphosphatase couple irreversible nucleotide hydrolysis steps to the installation of functional centers. Nuclear stages highlight how a conserved RNA-processing complex, the rixosome, couples large-scale RNA conformational changes with pre–ribosomal RNA processing by the RNA degradation machinery. Our ensemble of human pre-60 S particles provides a rich foundation with which to elucidate the molecular principles of ribosome formation.

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Metadata

Authors
Vanden Broeck, A., & Klinge, S.
Affiliations
  • Laboratory of Protein and Nucleic Acid Chemistry, The Rockefeller University, New York, NY 10065, USA.
  • Rockefeller University (US)
Corresponding author
Klinge, Sebastian
ORCID
Venue
Science
Publisher
American Association for the Advancement of Science (AAAS)
Published
2023-07-07
Volume
381
Issue
6653
Pages
eadh3892-eadh3892
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
DOI
10.1126/science.adh3892
PMC
PMC10054963
OpenAlex
W4383313666
Cited by
65
References
2
Citations by year
2026: 23 · 2025: 21 · 2024: 13 · 2023: 8
FWCI
5.79
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion)
  • ORBi (University of Liège) (submittedVersion, cc-by-nc-nd)
Funders
  • G. Harold and Leila Y. Mathers Foundation
  • National Institutes of Health
  • University of California, San Francisco
  • National Institute of General Medical Sciences (R01GM129325)
  • National Institute of Allergy and Infectious Diseases
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords
ribosome assembly, assembly factors, nucleolus, pre-rRNA processing, RNA conformational change, nucleotide hydrolysis, cryo-EM structure, human ribosome

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