Figure 3.
Regulatory stalling points in the translational cycle leading to stress granule (SG) formation. A closed-loop messenger RNA (mRNA) can stall at different points in the translation cycle, resulting in messenger ribonucleoproteins (mRNPs) of different composition eligible for condensation (mediated by GTP-activating protein-binding protein 1 [G3BP]) into SGs. Type I, or canonical SGs, result when eukaryotic initiation factor 2α (eIF2α) phosphorylation inhibits recharging of eIF2•GTP-Met-tRNAi Met, resulting in mRNPs that lack eIF2/5. Type II SGs form when eIF4A activities are inhibited and can be induced in cells lacking phospho-eIF2α, generating SGs that contain eIF2/5. Type III SGs result from xenobiotic stress, and lack eIF3. The mechanism shown here is hypothetical. Not shown are hyperosmotic/G3BP-independent SGs thought to arise from molecular crowding.