TY - JOUR
T1 - Coexisting Liquid Phases Underlie Nucleolar Subcompartments
AU - Feric, Marina
AU - Vaidya, Nilesh
AU - Harmon, Tyler S.
AU - Mitrea, Diana M.
AU - Zhu, Lian
AU - Richardson, Tiffany M.
AU - Kriwacki, Richard W.
AU - Pappu, Rohit V.
AU - Brangwynne, Clifford P.
N1 - Funding Information:
We thank members of the C.P.B. lab for discussions and Adrienne Fung for preliminary work on surface tension measurements. We acknowledge funding from the Princeton Center for Complex Materials, a MRSEC supported by NSF grant DMR 1420541. This work was also supported by an NIH Director’s New Innovator Award (1DP2GM105437-01 to C.P.B.), an NSF CAREER award (1253035 to C.P.B.), a Helen Hay Whitney Fellowship (to N.V.), an NSF grant (MCB 1121867 to R.V.P.), NIH grants (5RO1NS056114 to R.V.P. and 5R01GM115634 to R.W.K.), an NCI Cancer Center Support grant (P30CA21765 at St. Jude Children’s Research Hospital to R.W.K.), and ALSAC (R.W.K.).
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/6/16
Y1 - 2016/6/16
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cell.2016.04.047
DO - 10.1016/j.cell.2016.04.047
M3 - Article
C2 - 27212236
AN - SCOPUS:84975100086
SN - 0092-8674
VL - 165
SP - 1686
EP - 1697
JO - Cell
JF - Cell
IS - 7
ER -