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

TitleControlling the material properties and rRNA processing function of the nucleolus using light.
Publication TypeJournal Article
Year of Publication2019
AuthorsZhu, L, Richardson, TM, Wacheul, L, Wei, M-T, Feric, M, Whitney, G, Lafontaine, DLJ, Brangwynne, CP
JournalProc Natl Acad Sci U S A
Volume116
Issue35
Pagination17330-17335
Date Published2019 08 27
ISSN1091-6490
KeywordsAnimals, Cell Nucleolus, Mice, NIH 3T3 Cells, Optogenetics, RNA Processing, Post-Transcriptional, RNA, Ribosomal, Xenopus laevis
Abstract

<p>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.</p>

DOI10.1073/pnas.1903870116
Alternate JournalProc Natl Acad Sci U S A
PubMed ID31399547
PubMed Central IDPMC6717270
Grant ListU01 DA040601 / DA / NIDA NIH HHS / United States
/ HHMI / Howard Hughes Medical Institute / United States