Controlling the material properties and rRNA processing function of the nucleolus using light.
condensate
liquid–liquid phase separation
material properties
nucleolus
transcription
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
27 08 2019
27 08 2019
Historique:
pubmed:
11
8
2019
medline:
25
3
2020
entrez:
11
8
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31399547
pii: 1903870116
doi: 10.1073/pnas.1903870116
pmc: PMC6717270
doi:
Substances chimiques
RNA, Ribosomal
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
17330-17335Subventions
Organisme : NIDA NIH HHS
ID : U01 DA040601
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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