TY - JOUR
T1 - Thermodynamics and kinetics of phase separation of protein-RNA mixtures by a minimal model
AU - Joseph, Jerelle A.
AU - Espinosa, Jorge R.
AU - Sanchez-Burgos, Ignacio
AU - Garaizar, Adiran
AU - Frenkel, Daan
AU - Collepardo-Guevara, Rosana
N1 - Publisher Copyright:
© 2021
PY - 2021/4/6
Y1 - 2021/4/6
N2 - Intracellular liquid-liquid phase separation 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 liquid-liquid phase separation of protein-RNA mixtures. We demonstrate that at low to moderate concentrations, RNA enhances the stability of RNA-binding protein 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 assess 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.
AB - Intracellular liquid-liquid phase separation 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 liquid-liquid phase separation of protein-RNA mixtures. We demonstrate that at low to moderate concentrations, RNA enhances the stability of RNA-binding protein 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 assess 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.
UR - http://www.scopus.com/inward/record.url?scp=85101347678&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85101347678&partnerID=8YFLogxK
U2 - 10.1016/j.bpj.2021.01.031
DO - 10.1016/j.bpj.2021.01.031
M3 - Article
C2 - 33571491
AN - SCOPUS:85101347678
SN - 0006-3495
VL - 120
SP - 1219
EP - 1230
JO - Biophysical Journal
JF - Biophysical Journal
IS - 7
ER -