Chronic stress disrupts the network among stress granules, P-bodies, and motor proteins

Abstract

Stress granules (SGs) are dynamic RNA condensates that assemble rapidly in response to cellular stress following translational arrest, thereby promoting adaptation and influencing disease pathogenesis. Although SG assembly and disassembly during acute stress have been extensively characterized, their regulation under chronic stress remains poorly understood. We previously showed that chronic stress preconditioning suppresses the earliest stages of SG assembly through translation-dependent mechanisms. Whether chronic stress also impairs subsequent SG maturation has remained unknown. Here, we demonstrate that chronic stress limits SG maturation by disrupting the MYH9-dependent interaction network centered on the core SG nucleator G3BP1. Loss of this interaction reduces SG size and impairs docking between SGs and processing bodies (PBs), thereby restricting the maturation of nascent SGs. In parallel, chronic stress decreases expression of the SG nucleator UBAP2L, an essential regulator of SG-PB docking, further exacerbating these defects. Together, our findings identify chronic stress as a regulator of the MYH9-G3BP1-UBAP2L axis and reveal that chronic stress inhibits SG maturation through translation-independent mechanisms.