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Coaching ribosome biogenesis from the nuclear periphery.

Yinyin Zhuang1, Xiangfu Guo2, Olga V Razorenova3

  • 1Department of Developmental and Cell Biology, University of California, Irvine; Irvine, CA 92697, United States.

Biorxiv : the Preprint Server for Biology
|July 1, 2024
PubMed
Summary

Nuclear envelope invaginations regulate ribosome production. Reshaping these nuclear deformations with nanopillars can control ribosome biogenesis, offering a potential therapeutic strategy for diseases linked to nuclear invagination.

Keywords:
Expansion MicroscopyNanopillarsNuclear deformationOrganellar interactionsRibosome biogenesis

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Area of Science:

  • Cell Biology
  • Biophysics
  • Cancer Research

Background:

  • Severe nuclear envelope invagination is observed in various diseases including cancers, aging, neurodegeneration, and infections.
  • The precise functional outcomes and biological significance of nuclear invaginations remain largely undetermined.

Purpose of the Study:

  • To elucidate the functional consequences of nuclear invagination.
  • To investigate the relationship between nuclear invagination and ribosome biogenesis.
  • To explore the potential of manipulating nuclear shape for therapeutic interventions.

Main Methods:

  • Utilized expansion microscopy to visualize physical interactions between nuclear invaginations and nucleoli.
  • Employed custom-designed nanopillars to control the curvature of nuclear invaginations in cultured cells.
  • Quantified ribosomal RNA and pre-ribosome levels in response to altered nuclear invagination curvature.

Main Results:

  • Demonstrated a direct correlation between the curvature of nuclear invaginations and ribosome biogenesis rates.
  • Showed that cells grown on low-curvature nanopillars exhibited repressed ribosome levels, particularly in breast cancer and progeria cells.
  • Identified that high-curvature invaginations reduce heterochromatin and increase nuclear pore complexes, thereby promoting ribosome biogenesis.

Conclusions:

  • Nuclear invagination curvature is a critical regulator of ribosome biogenesis.
  • Nuclear shape modulation via nanopillars can effectively control and potentially rescue overactivated ribosome biogenesis.
  • These findings provide a mechanistic link between nuclear deformation and cellular function, opening new avenues for disease treatment.