Translational shutdown as a response to stress exposure allows cells to survive. The inhibition of protein synthesis is mediated by the key regulatory mechanisms of phosphorylation of eukaryotic initiation factor 2 (eIF2α) and assembly of the eIF4F complex. Following translation arrest, discrete foci known as stress granules form in the cytoplasm. Stress granules comprise mRNAs from disassembled polysomes, messenger ribonucleoproteins, translation initiation complexes and RNA-binding proteins. Coupled to translational control, stress granule assembly and disassembly is highly dynamic, but the mechanisms remain poorly understood. In this issue (p. 927), Pavel Ivanov and co-workers use haploid human cells to address the stress-specific differences in the composition and assembly of stress granules. Upon oxidative stress, the cells form canonical stress granules; by contrast, some other stresses lead to the formation of non-canonical stress granules called stress foci. The authors show that UV-induced stress leads to the formation of granules that lack eIF4G and eIF3, and only weakly recruit poly(A) mRNAs. Further, the authors find differences in the eIF2α-phosphorylation-dependent cell death response to various specific stresses. This study provides a comparative dataset for cellular responses to different stresses and for the formation and composition of stress granules, whose dysregulation is implicated in several human pathologies.
