bims-fascar Biomed News
on Phase separation and cellular architecture
Issue of 2021‒02‒14
two papers selected by
Victoria Yan
Max Planck Institute of Molecular Cell Biology and Genetics


  1. Curr Opin Cell Biol. 2021 Feb 09. pii: S0955-0674(21)00002-8. [Epub ahead of print]69 111-119
    Garcia-Cabau C, Salvatella X.
      Biomolecular condensates are mesoscopic biomolecular assemblies devoid of long range order that contribute to important cellular functions. They form reversibly, are stabilized by numerous but relatively weak intermolecular interactions, and their formation can be regulated by various cellular signals including changes in local concentration, post-translational modifications, energy-consuming processes, and biomolecular interactions. Condensates formed by liquid-liquid phase separation are initially liquid but are metastable relative to hydrogels or irreversible solids that have been associated with protein aggregation diseases and are stabilized by stronger, more permanent interactions. As a consequence of this, a series of cellular mechanisms are available to regulate not only biomolecular condensation but also the physical properties of the condensates.
    Keywords:  Alternative splicing; Biomolecular condensation; Liquid-liquid phase separation; Maturation; Post-translational modifications
    DOI:  https://doi.org/10.1016/j.ceb.2021.01.002
  2. Biophys J. 2021 Feb 08. pii: S0006-3495(21)00117-X. [Epub ahead of print]
    Joseph JA, Espinosa JR, Sanchez-Burgos I, Garaizar A, Frenkel D, Collepardo-Guevara R.
      Intracellular liquid-liquid phase separation (LLPS) enables the formation of biomolecular condensates, such as ribonucleoprotein granules, which play a crucial role in the spatiotemporal organization of biomolecules (e.g., proteins and RNAs). Here, we introduce a patchy-particle-polymer model to investigate LLPS of protein-RNA mixtures. We demonstrate that, at low to moderate concentrations, RNA enhances the stability of RNA-binding protein (RBP) condensates because it increases the molecular connectivity of the condensed-liquid phase. Importantly, we find that RNA can also accelerate the nucleation stage of phase separation. Additionally, we asses how the capacity of RNA to increase the stability of condensates is modulated by the relative protein-protein/protein-RNA binding strengths. We find that phase separation and multiphase organization of multicomponent condensates is favored when the RNA binds with higher affinity to the lower valency proteins in the mixture, than to the cognate higher valency proteins. Collectively, our results shed light on the roles of RNA in ribonucleoprotein granule formation and the internal structuring of stress granules. SIGNIFICANCE: The interior of cells contains several membraneless compartments that are composed of proteins and RNA. These compartments are formed and sustained by LLPS. Here, we introduce a minimal coarse-grained model to study LLPS of protein-RNA mixtures. We find that RNA can increase the stability of phase-separated compartments by enhancing the molecular connectivity of proteins. Additionally, our results show that RNA actively recruits proteins-accelerating the nucleation and fusion stages of LLPS. Interestingly, we find that spatial segregation within protein-RNA compartments is controlled by fine-tuning the interaction strengths and stoichiometries of components. Our model, therefore, provides a useful tool for building a comprehensive mechanistic and thermodynamic view of protein-RNA LLPS.
    DOI:  https://doi.org/10.1016/j.bpj.2021.01.031