The sequence grammar and interactions controlling the aging of protein biomolecular condensates

Biomolecular condensates play key roles in the cell by organizing and regulating important biochemical processes, including transcriptional regulation, RNA metabolism, ribosome biogenesis, and stress responses. While these assemblies are typically dynamic, some can undergo time-dependent aging into solid assemblies, which in certain cases has been linked to pathologies including neurodegenerative diseases. In this review, we focus on the mechanisms that drive condensate aging. In particular, we discuss how features of protein sequence, such as amino acid composition, interaction motifs, and post-translational modifications, influence condensate aging. We further highlight how interactions with RNA and lipid membranes modulate condensate behavior by altering interaction networks and interfacial properties.