ArticleProceedings of the National Academy of Sciences of the United States of America2022
Phase-separating RNA-binding proteins form heterogeneous distributions of clusters in subsaturated solutions.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 181 papers.
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Who cites it
181 citing papers in PubMed.
- Uncovering essential RNA components of fusion oncoprotein condensates using bicon-seq.The EMBO journal · 2026Article
- Chain collapse, reduced dielectric, and water release drive protein phase separation.Biophysical journal · 2026Article
- α-Synuclein Forms Distinct Micelle-Like Assemblies at Low Ionic Strengths.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Biomolecular condensates can function as inherent catalysts.Molecular cell · 2026Article
- Backbone Hydrogen Bonding as a Determinant of Condensate Material States.Journal of the American Chemical Society · 2026Article
- Sticker Valence Governs Chain Collapse and Liquid-Liquid Phase Separation in Peptide-Inspired Associative Polymers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Beyond equilibrium in biomolecular phase separation.Nature structural & molecular biology · 2026Article
- Current Challenges of Transcription Compartmentalization Research.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Nanoclustering of a plant transcription factor enables strong yet specific DNA binding.Science advances · 2026Article
- Purification and preparation of Marchantia polymorpha Auxin Response Factor 2 for phase separation studies.FEBS open bio · 2026Article
- Distinguishing near- versus off-critical phase behaviors of intrinsically disordered proteins.Reports on progress in physics. Physical Society (Great Britain) · 2026Article
- Entropic Charge Separation as a General Mechanism Arresting Nanoscale Condensate Coarsening.Physical review letters · 2026Article
- Mapping interactions between disordered regions reveals promiscuity in biomolecular condensate formation.Nature communications · 2026Article
- Protein•DNA mesh assembly drives dsDNA-specific and duplex length-dependent activation of cGAS.bioRxiv : the preprint server for biology · 2026Article
- Nascent protein retention at polysomes reduces kinetic barriers to self-assembly.bioRxiv : the preprint server for biology · 2026Article
- Nucleation Kinetics Reveals a Distinct Biological Function Space of Biomolecular Condensates.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- FuzDrop: sequence-based prediction of the propensity of proteins for liquid-liquid phase separation and aggregation.Nature protocols · 2026Review
- RNA-binding proteins: a comprehensive review of multifaceted regulatory mechanisms in neuroinflammation and implications in the pathogenesis of neurological disorders.Journal of neuroinflammation · 2026Review
- Visualization of oligomerization, clustering, and density transition of intrinsically disordered proteins.National science review · 2026Article
- Effects of Arginine on Hierarchical Protein Aggregation.The protein journal · 2026Article
121 more citing papers are in PubMed but not listed here.
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13 authors.
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Abstract
Macromolecular phase separation is thought to be one of the processes that drives the formation of membraneless biomolecular condensates in cells. The dynamics of phase separation are thought to follow the tenets of classical nucleation theory, and, therefore, subsaturated solutions should be devoid of clusters with more than a few molecules. We tested this prediction using in vitro biophysical studies to characterize subsaturated solutions of phase-separating RNA-binding proteins with intrinsically disordered prion-like domains and RNA-binding domains. Surprisingly, and in direct contradiction to expectations from classical nucleation theory, we find that subsaturated solutions are characterized by the presence of heterogeneous distributions of clusters. The distributions of cluster sizes, which are dominated by small species, shift continuously toward larger sizes as protein concentrations increase and approach the saturation concentration. As a result, many of the clusters encompass tens to hundreds of molecules, while less than 1% of the solutions are mesoscale species that are several hundred nanometers in diameter. We find that cluster formation in subsaturated solutions and phase separation in supersaturated solutions are strongly coupled via sequence-encoded interactions. We also find that cluster formation and phase separation can be decoupled using solutes as well as specific sets of mutations. Our findings, which are concordant with predictions for associative polymers, implicate an interplay between networks of sequence-specific and solubility-determining interactions that, respectively, govern cluster formation in subsaturated solutions and the saturation concentrations above which phase separation occurs.
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