期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 116, 期 35, 页码 17330-17335出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1903870116
关键词
nucleolus; material properties; transcription; liquid-liquid phase separation; condensate
资金
- Howard Hughes Medical Institute
- NIH 4D Nucleome Program [U01 DA040601]
- Princeton Center for Complex Materials
- NSF-supported Materials Research Science and Engineering Center [DMR 1420541]
- NSF CAREER award [1253035]
- NSF [PHY-1607612]
- NSF Graduate Research Fellowship Program [DCE-1656466]
- Fonds de la Recherche Scientifique
- Universite Libre de Bruxelles
- Fonds Jean Brachet
- Region Wallonne (DGO6)
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.
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