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bioRxiv · 10.1101/600601

Interplay Between Short-range Attraction and Long-range Repulsion Controls Reentrant Liquid Condensation of Ribonucleoprotein-RNA Complexes

Alshareedah, I.·Kaur, T.·Ngo, J.·Seppala, H.·Djomnang Kounatse, L.-A.·Wang, W.·Moosa, M. M.·Banerjee, P. R.
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Abstract

In eukaryotic cells, ribonucleoproteins (RNPs) form mesoscale condensates by liquid-liquid phase separation that play essential roles in subcellular dynamic compartmentalization. The formation and dissolution of many RNP condensates are finely dependent on the RNA-to-RNP ratio, giving rise to a window-like phase separation behavior. This is commonly referred to as reentrant liquid condensation (RLC). Here, using RNP-inspired polypeptides with low-complexity RNA-binding sequences as well as the C-terminal disordered domain of the ribonucleoprotein FUS as model systems, we investigate the molecular driving forces underlying this non-monotonous phase transition. We show that an interplay between short-range cation-{pi} attractions and long-range electrostatic forces governs the heterotypic RLC of RNP-RNA complexes. Short-range attractions, which can be encoded by both polypeptide chain primary sequence and nucleic acid base sequence, are activated by RNP-RNA condensate formation. After activation, the short-range forces regulate material properties of polypeptide-RNA condensates and subsequently oppose their reentrant dissolution. In the presence of excess RNA, a competition between short-range attraction and long-range electrostatic repulsion drives the formation of a colloid-like cluster phase. With increasing short-range attraction, the fluid dynamics of the cluster phase is arrested, leading to the formation of a colloidal gel. Our results reveal that phase behavior, supramolecular organization, and material states of RNP-RNA assemblies are controlled by a dynamic interplay between molecular interactions at different length scales.

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Alshareedah, I., Kaur, T., Ngo, J., Seppala, H., Djomnang Kounatse, L.-A., Wang, W., Moosa, M. M., Banerjee, P. R.. 2019-04-06. Interplay Between Short-range Attraction and Long-range Repulsion Controls Reentrant Liquid Condensation of Ribonucleoprotein-RNA Complexes. https://doi.org/10.1101/600601

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