Stress granules and RNA-binding proteins in cellular senescence: a modular perspective on stress adaptation and...

Cellular senescence is a complex stress response characterized not only by stable growth arrest but also by chromatin remodeling, altered proteostasis, metabolic adaptation, innate immune activation, and the senescence-associated secretory phenotype. Stress granules (SGs) are dynamic membraneless ribonucleoprotein condensates that form during translational stress and regulate mRNA triage, signaling and recovery. While both senescence and SGs represent important features of cellular stress response, the mechanisms underlying their intersection remain poorly defined. This review examines how the biology of SGs and RNA-binding proteins (RBPs) regulate senescence, with particular emphasis on stress granule-induced inflammation associated with SASP, activation of cGAS-STING, induction of NF- κB signaling, and interferon response. We discuss the differential ability of senescence inducers to generate canonical SGs and why SG formation does not necessarily result in global translational shutdown. In addition, we examine the potential roles of SG-associated RBPs, including G3BP1/2, TIA1/TIAR, CAPRIN1, USP10, HuR, ZFP36 family, FXR1, and TDP-43 together with methodological standards for identifying SGs in senescence. We present a stage-resolved modular framework describing the context-dependent functions of SG-associated RBPs throughout senescence progression and discuss therapeutic opportunities. Overall, this review suggests that stress granules and associated RNA-binding proteins should be considered context-dependent components in inflammation-driven senescence, rather than universal inducers of senescence onset.