Controlling the material properties and rRNA processing function of the nucleolus using light

Lian Zhu, Tiffany M. Richardson, Ludivine Wacheul, Ming Tzo Wei, Marina Feric, Gena Whitney, Denis L.J. Lafontaine, Clifford P. Brangwynne

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

The nucleolus is a prominent nuclear condensate that plays a central role in ribosome biogenesis by facilitating the transcription and processing of nascent ribosomal RNA (rRNA). A number of studies have highlighted the active viscoelastic nature of the nucleolus, whose material properties and phase behavior are a consequence of underlying molecular interactions. However, the ways in which the material properties of the nucleolus impact its function in rRNA biogenesis are not understood. Here we utilize the Cry2olig optogenetic system to modulate the viscoelastic properties of the nucleolus. We show that above a threshold concentration of Cry2olig protein, the nucleolus can be gelled into a tightly linked, low mobility meshwork. Gelled nucleoli no longer coalesce and relax into spheres but nonetheless permit continued internal molecular mobility of small proteins. These changes in nucleolar material properties manifest in specific alterations in rRNA processing steps, including a buildup of larger rRNA precursors and a depletion of smaller rRNA precursors. We propose that the flux of processed rRNA may be actively tuned by the cell through modulating nucleolar material properties, which suggests the potential of materials-based approaches for therapeutic intervention in ribosomopathies.

Original languageEnglish (US)
Pages (from-to)17330-17335
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number35
DOIs
StatePublished - Aug 27 2019

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Condensate
  • Liquid–liquid phase
  • Material properties
  • Nucleolus
  • Separation
  • Transcription

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