ArticleProceedings of the National Academy of Sciences of the United States of America2015
The disordered P granule protein LAF-1 drives phase separation into droplets with tunable viscosity and dynamics.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 747 papers.
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747 citing papers in PubMed, 1,330 citations in OpenAlex.
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- Progress toward linking single-molecule behavior and condensate material properties.Current opinion in structural biology · 2026Review
- Heat stress promotes GTBP-1 association with perinuclear P-bodies in the C. elegans germline.PLoS genetics · 2026Article
- Designed IDPs phase separate and mix or demix according to sequence designed parameters.bioRxiv : the preprint server for biology · 2026Article
- Fusion dynamics of viscoelastic droplets: Similarities and differences with shape recovery.Biophysical journal · 2026Article
- Biomimetic Coacervate Coatings: From Phase Separation Fundamentals to Advanced Biomedical Applications.Biomimetics (Basel, Switzerland) · 2026Review
- High-throughput identification of endogenous biomolecular condensates and phase-separating proteins.Nature protocols · 2026Review
- Advances in engineering and applications of synthetic phase-separated membraneless organelles in biotechnology.Synthetic and systems biotechnology · 2026Review
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- Hydration free energy is an incomplete predictor of globular protein incorporation into condensates.Biophysical journal · 2026Article
- Sticker Valence Governs Chain Collapse and Liquid-Liquid Phase Separation in Peptide-Inspired Associative Polymers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Programmable Multiphasic Condensates Formed via Evaporation-Induced Phase Separation of Minimal Peptide Model.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Bottom-up reconstruction of synthetic pyrenoids provides insights into the mechanisms and evolution of carbon concentration by EPYC1 proteins.Nature plants · 2026Article
- A machine learning framework for predicting and modulating condition-dependent protein phase separation.Nature communications · 2026Article
- CELF2 promotes 4R Tau splicing via nuclear clustering and drives cognitive dysfunction in tauopathy models.Nature communications · 2026Article
687 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
P granules and other RNA/protein bodies are membrane-less organelles that may assemble by intracellular phase separation, similar to the condensation of water vapor into droplets. However, the molecular driving forces and the nature of the condensed phases remain poorly understood. Here, we show that the Caenorhabditis elegans protein LAF-1, a DDX3 RNA helicase found in P granules, phase separates into P granule-like droplets in vitro. We adapt a microrheology technique to precisely measure the viscoelasticity of micrometer-sized LAF-1 droplets, revealing purely viscous properties highly tunable by salt and RNA concentration. RNA decreases viscosity and increases molecular dynamics within the droplet. Single molecule FRET assays suggest that this RNA fluidization results from highly dynamic RNA-protein interactions that emerge close to the droplet phase boundary. We demonstrate than an N-terminal, arginine/glycine rich, intrinsically disordered protein (IDP) domain of LAF-1 is necessary and sufficient for both phase separation and RNA-protein interactions. In vivo, RNAi knockdown of LAF-1 results in the dissolution of P granules in the early embryo, with an apparent submicromolar phase boundary comparable to that measured in vitro. Together, these findings demonstrate that LAF-1 is important for promoting P granule assembly and provide insight into the mechanism by which IDP-driven molecular interactions give rise to liquid phase organelles with tunable properties.
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