@article{155ae5aa67fd4f6bb0b6d2999d810f29,
title = "Controlling the material properties and rRNA processing function of the nucleolus using light",
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.",
keywords = "Condensate, Liquid–liquid phase, Material properties, Nucleolus, Separation, Transcription",
author = "Lian Zhu and Richardson, {Tiffany M.} and Ludivine Wacheul and Wei, {Ming Tzo} and Marina Feric and Gena Whitney and Lafontaine, {Denis L.J.} and Brangwynne, {Clifford P.}",
note = "Funding Information: ACKNOWLEDGMENTS. We thank David Sanders, Amy Strom, Josh Riback, and other members of the C.P.B. laboratory for help with experiments and comments on the manuscript. This work was supported by the Howard Hughes Medical Institute and grants from the NIH 4D Nucleome Program (U01 DA040601), the Princeton Center for Complex Materials, the NSF-supported Materials Research Science and Engineering Center (DMR 1420541), an NSF CAREER award (1253035), NSF Grant PHY-1607612, and the NSF Graduate Research Fellowship Program (DCE-1656466). D.L.J.L. and L.W. were supported by Fonds de la Recherche Scientifique, Fonds Jean Brachet, R{\'e}gion Wallonne (DGO6), and the Universit{\'e} Libre de Bruxelles. Funding Information: . We thank David Sanders, Amy Strom, Josh Riback, and other members of the C.P.B. laboratory for help with experiments and comments on the manuscript. This work was supported by the Howard Hughes Medical Institute and grants from the NIH 4D Nucleome Program (U01 DA040601), the Princeton Center for Complex Materials, the NSF-supported Materials Research Science and Engineering Center (DMR 1420541), an NSF CAREER award (1253035), NSF Grant PHY-1607612, and the NSF Graduate Research Fellowship Program (DCE-1656466). D.L.J.L. and L.W. were supported by Fonds de la Recherche Scientifique, Fonds Jean Brachet, R?gion Wallonne (DGO6), and the Universit? Libre de Bruxelles. Publisher Copyright: {\textcopyright} 2019 National Academy of Sciences. All rights reserved.",
year = "2019",
month = aug,
day = "27",
doi = "10.1073/pnas.1903870116",
language = "English (US)",
volume = "116",
pages = "17330--17335",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "35",
}