Coexisting Liquid Phases Underlie Nucleolar Subcompartments

Marina Feric, Nilesh Vaidya, Tyler S. Harmon, Diana M. Mitrea, Lian Zhu, Tiffany M. Richardson, Richard W. Kriwacki, Rohit V. Pappu, Clifford P. Brangwynne

Research output: Contribution to journalArticle

426 Scopus citations

Abstract

The nucleolus and other ribonucleoprotein (RNP) bodies are membrane-less organelles that appear to assemble through phase separation of their molecular components. However, many such RNP bodies contain internal subcompartments, and the mechanism of their formation remains unclear. Here, we combine in vivo and in vitro studies, together with computational modeling, to show that subcompartments within the nucleolus represent distinct, coexisting liquid phases. Consistent with their in vivo immiscibility, purified nucleolar proteins phase separate into droplets containing distinct non-coalescing phases that are remarkably similar to nucleoli in vivo. This layered droplet organization is caused by differences in the biophysical properties of the phases - particularly droplet surface tension - which arises from sequence-encoded features of their macromolecular components. These results suggest that phase separation can give rise to multilayered liquids that may facilitate sequential RNA processing reactions in a variety of RNP bodies.

Original languageEnglish (US)
Pages (from-to)1686-1697
Number of pages12
JournalCell
Volume165
Issue number7
DOIs
StatePublished - Jun 16 2016

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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    Feric, M., Vaidya, N., Harmon, T. S., Mitrea, D. M., Zhu, L., Richardson, T. M., Kriwacki, R. W., Pappu, R. V., & Brangwynne, C. P. (2016). Coexisting Liquid Phases Underlie Nucleolar Subcompartments. Cell, 165(7), 1686-1697. https://doi.org/10.1016/j.cell.2016.04.047