RNA condensates in oocyte adaptation to quiescence and stress

Gene expression must be robustly controlled in the face of environmental challenges and cellular activity changes. How the millions of transcripts that coexist in the cytosol coordinate their expression to cellular activities and environments remains to be addressed. Here, using C. elegans oogenesis as a model, we focused on RNAs that co-assemble with regulatory binding proteins (RBP) into RNA condensates upon quiescence and across temperature changes.Taking advantage of a cutting-edge approach that we previously developed (Hubstenberger et al., Mol Cell 2017; Cardona et al., Cell 2023), and that combines the purification sequencing of RNA condensates with single molecule RNA imaging, we investigated (1) the structural mechanisms that drive RNA supramolecular organization, and (2) the emerging properties that determine condensate functionalities and RNA fate. We found that maternal RNA super-assemblies are transcriptome-wide reservoirs that buffer the accumulation of repressed mRNAs through a concentration dependent phase separation, and sort RNAs depending on sequence identity. This buffering capacity controls RNA:RBP and RNA:RNA stoichiometries and maintains cellular homeostasis in the face of temperature changes. The sorting selectivity across RNA diversity was the result of RNA homotypic self-assemblies, and allowed each RNA species to be regulated independently across oocyte differentiation, during activity switches, or in adaptation to diverse environments. Condensates also structurally protected RNAs from pathological aggregation upon stress, and preserved the ability of mRNAs to quickly solubilize when optimal condition resumed. Altogether, physiological condensates structurally protect RNAs from stress induced pathological aggregation, while their buffering and sorting capacity provide compositional control of the cytosolic transcriptome that is adapted to both cellular activity and environmental changes.