Translation Landscape of Stress Granules

Abstract

Stress granules, cytoplasmic assemblies of RNA-binding proteins and mRNAs formed during cellular stress, are implicated in translational control. However, their exact functions remain elusive. Here, we employed cryogenic correlative light and electron microscopy to visualize stress granules in their native environment and reconstructed them in 3D using tomography. This approach provided the first quantitative and spatial analysis of the translational machinery within stress granules. Our findings suggest that stress granules have a limited impact on global translation regulation but serve to protect small ribosomal subunits and pre-initiation complexes (PICs) from degradation. Numerical simulations based on a phase-field model accurately reproduced the spatial distribution of ribosomal components inside and outside the stress granules, shedding light on the thermodynamic principles governing this process.