Stress granules: Guardians of cellular health and triggers of disease

Stress granules are membraneless organelles that serve as a protective cellular response to external stressors by sequestering non-translating messenger RNAs (mRNAs) and regulating protein synthesis. Stress granules formation mechanism is conserved across species, from yeast to mammals, and they play a critical role in minimizing cellular damage during stress. Composed of heterogeneous ribonucleoprotein complexes, stress granules are enriched not only in mRNAs but also in noncoding RNAs and various proteins, including translation initiation factors and RNA-binding proteins. Genetic mutations affecting stress granule assembly and disassembly can lead to abnormal stress granule accumulation, contributing to the progression of several diseases. Recent research indicates that stress granule dynamics are pivotal in determining their physiological and pathological functions, with acute stress granule formation offering protection and chronic stress granule accumulation being detrimental. This review focuses on the multifaceted roles of stress granules under diverse physiological conditions, such as regulation of mRNA transport, mRNA translation, apoptosis, germ cell development, phase separation processes that govern stress granule formation, and their emerging implications in pathophysiological scenarios, such as viral infections, cancer, neurodevelopmental disorders, neurodegeneration, and neuronal trauma.