Stressful initiations

Abstract

Stress granules (SGs) are phase-dense particles that appear in the cytoplasm of eukaryotic cells that have been exposed to environmental stress(e.g. heat, oxidative conditions, hyperosmolarity and UV irradiation). SG assembly is a consequence of abortive translational initiation: SGs appear when translation is initiated in the absence of eIF2-GTP-tRNAiMet, the ternary complex that normally loads tRNAiMet onto the small ribosomal subunit. Stress-induced depletion of eIF2-GTP-tRNAiMet allows the related RNA-binding proteins TIA-1 and TIAR to promote the assembly of eIF2-eIF5-deficient preinitiation complexes, the core constituents of SGs. The mRNP components that make up the SG are in a dynamic equilibrium with polysomes. As such, the SG appears to constitute a metabolic domain through which mRNPs are continually routed and subjected to triage — they are first monitored for integrity and composition, and then sorted for productive translational initiation or targeted degradation.