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King MR, Ruff KM, Lin AZ, Pant A, Farag M, Lalmansingh JM, Wu T, Fossat MJ, Ouyang W, Lew MD, Lundberg E, Vahey MD, Pappu RV
Cell 187 (8) 1889-1906.e24 [2024-04-11; online 2024-03-18]
Nucleoli are multicomponent condensates defined by coexisting sub-phases. We identified distinct intrinsically disordered regions (IDRs), including acidic (D/E) tracts and K-blocks interspersed by E-rich regions, as defining features of nucleolar proteins. We show that the localization preferences of nucleolar proteins are determined by their IDRs and the types of RNA or DNA binding domains they encompass. In vitro reconstitutions and studies in cells showed how condensation, which combines binding and complex coacervation of nucleolar components, contributes to nucleolar organization. D/E tracts of nucleolar proteins contribute to lowering the pH of co-condensates formed with nucleolar RNAs in vitro. In cells, this sets up a pH gradient between nucleoli and the nucleoplasm. By contrast, juxta-nucleolar bodies, which have different macromolecular compositions, featuring protein IDRs with very different charge profiles, have pH values that are equivalent to or higher than the nucleoplasm. Our findings show that distinct compositional specificities generate distinct physicochemical properties for condensates.
PubMed 38503281
DOI 10.1016/j.cell.2024.02.029
Crossref 10.1016/j.cell.2024.02.029
mid: NIHMS2044799
pmc: PMC11938373
pii: S0092-8674(24)00232-0