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Controlling the material properties and rRNA processing function of the nucleolus using light.
Proc Natl Acad Sci U S A 2019; 116(35):17330-17335PN

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.

Authors+Show Affiliations

Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544.Department of Molecular Biology, Princeton University, Princeton, NJ 08544.RNA Molecular Biology, Université Libre de Bruxelles Cancer Research Center, Center for Microscopy and Molecular Imaging, Fonds de la Recherche Scientifique, Université Libre de Bruxelles, 1070 Bruxelles, Belgium.Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544.Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544.Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544.RNA Molecular Biology, Université Libre de Bruxelles Cancer Research Center, Center for Microscopy and Molecular Imaging, Fonds de la Recherche Scientifique, Université Libre de Bruxelles, 1070 Bruxelles, Belgium.Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544; cbrangwy@princeton.edu. Howard Hughes Medical Institute, Princeton University, Princeton, NJ 08544.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31399547

Citation

Zhu, Lian, et al. "Controlling the Material Properties and rRNA Processing Function of the Nucleolus Using Light." Proceedings of the National Academy of Sciences of the United States of America, vol. 116, no. 35, 2019, pp. 17330-17335.
Zhu L, Richardson TM, Wacheul L, et al. Controlling the material properties and rRNA processing function of the nucleolus using light. Proc Natl Acad Sci USA. 2019;116(35):17330-17335.
Zhu, L., Richardson, T. M., Wacheul, L., Wei, M. T., Feric, M., Whitney, G., ... Brangwynne, C. P. (2019). Controlling the material properties and rRNA processing function of the nucleolus using light. Proceedings of the National Academy of Sciences of the United States of America, 116(35), pp. 17330-17335. doi:10.1073/pnas.1903870116.
Zhu L, et al. Controlling the Material Properties and rRNA Processing Function of the Nucleolus Using Light. Proc Natl Acad Sci USA. 2019 Aug 27;116(35):17330-17335. PubMed PMID: 31399547.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Controlling the material properties and rRNA processing function of the nucleolus using light. AU - Zhu,Lian, AU - Richardson,Tiffany M, AU - Wacheul,Ludivine, AU - Wei,Ming-Tzo, AU - Feric,Marina, AU - Whitney,Gena, AU - Lafontaine,Denis L J, AU - Brangwynne,Clifford P, Y1 - 2019/08/09/ PY - 2020/02/09/pmc-release PY - 2019/8/11/pubmed PY - 2019/8/11/medline PY - 2019/8/11/entrez KW - condensate KW - liquid–liquid phase separation KW - material properties KW - nucleolus KW - transcription SP - 17330 EP - 17335 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc. Natl. Acad. Sci. U.S.A. VL - 116 IS - 35 N2 - 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. SN - 1091-6490 UR - https://www.unboundmedicine.com/medline/citation/31399547/Controlling_the_material_properties_and_rRNA_processing_function_of_the_nucleolus_using_light L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=31399547 DB - PRIME DP - Unbound Medicine ER -