Sequence-encoded and composition-dependent protein-RNA interactions control multiphasic condensate morphologies

Taranpreet Kaur, Muralikrishna Raju, Ibraheem Alshareedah, Richoo B. Davis, Davit A. Potoyan () and Priya R. Banerjee ()
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Taranpreet Kaur: University at Buffalo
Muralikrishna Raju: Iowa State University
Ibraheem Alshareedah: University at Buffalo
Richoo B. Davis: University at Buffalo
Davit A. Potoyan: Iowa State University
Priya R. Banerjee: University at Buffalo

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: Abstract Multivalent protein-protein and protein-RNA interactions are the drivers of biological phase separation. Biomolecular condensates typically contain a dense network of multiple proteins and RNAs, and their competing molecular interactions play key roles in regulating the condensate composition and structure. Employing a ternary system comprising of a prion-like polypeptide (PLP), arginine-rich polypeptide (RRP), and RNA, we show that competition between the PLP and RNA for a single shared partner, the RRP, leads to RNA-induced demixing of PLP-RRP condensates into stable coexisting phases—homotypic PLP condensates and heterotypic RRP-RNA condensates. The morphology of these biphasic condensates (non-engulfing/ partial engulfing/ complete engulfing) is determined by the RNA-to-RRP stoichiometry and the hierarchy of intermolecular interactions, providing a glimpse of the broad range of multiphasic patterns that are accessible to these condensates. Our findings provide a minimal set of physical rules that govern the composition and spatial organization of multicomponent and multiphasic biomolecular condensates.

Date: 2021
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DOI: 10.1038/s41467-021-21089-4

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