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

Kaur, Taranpreet; Raju, Muralikrishna; Alshareedah, Ibraheem; Davis, Richoo B.; Potoyan, Davit A.; Banerjee, Priya R.

doi:10.1038/s41467-021-21089-4

Cited by 183 publications

(227 citation statements)

References 94 publications

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“…Considering the role that arginine residues play in LLPS, Kaur et al . [ 66 ] extended these studies to examine the behaviour of a three-component system consisting of a PrLD, an arginine-rich polypeptide (RRP), and RNA. The behaviour of each of these individual components is affected by the relative concentrations of the other two.…”

Section: The Underlying Chemical and Physical Basis For Internal Organization Of Condensatesmentioning

confidence: 99%

“…The behaviour of each of these individual components is affected by the relative concentrations of the other two. Specifically, the presence of an RRP induces PrLD LLPS, whereas RNA can promote LLPS of RRPs but not of PrLDs, underscoring the importance of arginine in forming protein : RNA condensates [ 66 ]. These findings may be of relevance in C9-ALS/FTD, where arginine-rich DPRs are particularly toxic [ 67 – 74 ].…”

Section: The Underlying Chemical and Physical Basis For Internal Organization Of Condensatesmentioning

confidence: 99%

“…These findings may be of relevance in C9-ALS/FTD, where arginine-rich DPRs are particularly toxic [ 67 – 74 ]. Intriguingly, RRP : RNA condensates adopt an internal structure when one component is present in excess over the other, with the more abundant molecule residing on the surface of the condensate [ 66 ].…”

Section: The Underlying Chemical and Physical Basis For Internal Organization Of Condensatesmentioning

confidence: 99%

“…These results suggest that proteins with arginine-rich domains may act as nodes within condensate networks, coordinating interactions between various condensate components. In fact, when PrLD : RRP droplets were made at low PrLD concentrations, the addition of RNA sequestered the RRP away from these droplets, causing the PrLDs to dissociate [ 66 ]. However, when PrLD : RRP condensates were formed with high relative PrLD levels, the addition of RNA enabled the formation of RRP : RNA droplets, but PrLD condensates persisted, leading to a coexisting droplet network with distinct RRP : RNA condensates on the surface of the PrLD droplets [ 66 ].…”

Section: The Underlying Chemical and Physical Basis For Internal Organization Of Condensatesmentioning

confidence: 99%

“…In addition to this associative droplet network, Kaur et al . [ 66 ] could also generate condensate architectures with immiscible layers by varying the ratio of RNA to RRP.…”

Section: The Underlying Chemical and Physical Basis For Internal Organization Of Condensatesmentioning

confidence: 99%

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Higher-order organization of biomolecular condensates

et al. 2021

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A guiding principle of biology is that biochemical reactions must be organized in space and time. One way this spatio-temporal organization is achieved is through liquid–liquid phase separation (LLPS), which generates biomolecular condensates. These condensates are dynamic and reactive, and often contain a complex mixture of proteins and nucleic acids. In this review, we discuss how underlying physical and chemical processes generate internal condensate architectures. We then outline the diverse condensate architectures that are observed in biological systems. Finally, we discuss how specific condensate organization is critical for specific biological functions.

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Section: The Underlying Chemical and Physical Basis For Internal Organization Of Condensatesmentioning

confidence: 99%

Section: The Underlying Chemical and Physical Basis For Internal Organization Of Condensatesmentioning

confidence: 99%

Section: The Underlying Chemical and Physical Basis For Internal Organization Of Condensatesmentioning

confidence: 99%

Section: The Underlying Chemical and Physical Basis For Internal Organization Of Condensatesmentioning

confidence: 99%

“…In addition to this associative droplet network, Kaur et al . [ 66 ] could also generate condensate architectures with immiscible layers by varying the ratio of RNA to RRP.…”

Section: The Underlying Chemical and Physical Basis For Internal Organization Of Condensatesmentioning

confidence: 99%

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Higher-order organization of biomolecular condensates

et al. 2021

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Programmable Zwitterionic Droplets as Biomolecular Sorters and Model of Membraneless Organelles

et al. 2021

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Increasing evidence indicates that cells can regulate biochemical functions in time and space by generating membraneless compartments with well‐defined mesoscopic properties. One important mechanism underlying this control is simple coacervation driven by associative disordered proteins that encode multivalent interactions. Inspired by these observations, programmable droplets based on simple coacervation of responsive synthetic polymers that mimic the “stickers‐and‐spacers” architecture of biological disordered proteins are developed. Zwitterionic polymers that undergo an enthalpy‐driven liquid–liquid phase separation process and form liquid droplets that remarkably exclude most molecules are developed. Starting from this reference material, different functional groups in the zwitterionic polymer are progressively added to encode an increasing number of different intermolecular interactions. This strategy allowed the multiple emerging properties of the droplets to be controlled independently, such as stimulus‐responsiveness, polarity, selective uptake of client molecules, fusion times, and miscibility. By exploiting this high programmability, a model of cellular compartmentalization is reproduced and droplets capable of confining different molecules in space without physical barriers are generated. Moreover, these biomolecular sorters are demonstrated to be able to localize, separate, and enable the detection of target molecules even within complex mixtures, opening attractive applications in bioseparation, and diagnostics.

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Molecular determinants for the layering and coarsening of biological condensates

Latham

Zhang

2022

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Many membraneless organelles, or biological condensates, form through phase separation, and play key roles in signal sensing and transcriptional regulation. While the functional importance of these condensates has inspired many studies to characterize their stability and spatial organization, the underlying principles that dictate these emergent properties are still being uncovered. In this review, we examine recent work on biological condensates, especially multicomponent systems. We focus on connecting molecular factors such as binding energy, valency, and stoichiometry with the interfacial tension, explaining the nontrivial interior organization in many condensates. We further discuss mechanisms that arrest condensate coalescence by lowering the surface tension or introducing kinetic barriers to stabilize the multidroplet state.

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

Cited by 183 publications

References 94 publications

Higher-order organization of biomolecular condensates

Higher-order organization of biomolecular condensates

Programmable Zwitterionic Droplets as Biomolecular Sorters and Model of Membraneless Organelles

Molecular determinants for the layering and coarsening of biological condensates

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