Integrated multi-omics reveals common properties underlying stress granule and P-body formation.

Non-membrane-bound compartments such as P-bodies (PBs) and stress granules (SGs) play important roles in the regulation of gene expression following environmental stresses. We have systematically and quantitatively determined the protein and mRNA composition of PBs and SGs formed before and after nutrient stress. We find that high molecular weight (HMW) complexes exist prior to glucose depletion that we propose may act as seeds for further condensation of proteins forming mature PBs and SGs. We identify an enrichment of proteins with low complexity and RNA binding domains, as well as long, structured mRNAs that are poorly translated following nutrient stress. Many proteins and mRNAs are shared between PBs and SGs including several multivalent RNA binding proteins that promote condensate interactions during liquid-liquid phase separation. We uncover numerous common protein and RNA components across PBs and SGs that support a complex interaction profile during the maturation of these biological condensates. These interaction networks represent a tuneable response to stress, highlighting previously unrecognized condensate heterogeneity. These studies therefore provide an integrated and quantitative understanding of the dynamic nature of key biological condensates.