stressgranules

Stress granules are membrane-less cytoplasmic ribonucleoprotein assemblies that form in response to cellular stress when translation initiation is inhibited. They contain untranslated mRNAs, stalled translation preinitiation complexes, and a variety of RNA-binding proteins. Stress granules are dynamic and reversible, forming through liquid-liquid phase separation and dissolving when the stress subsides.

Their formation is commonly linked to inhibition of translation initiation, often via phosphorylation of eIF2α by kinases such as PERK, GCN2, PKR, or HRI. This reduces the supply of ternary complexes needed for initiation, causing mRNAs and associated initiation factors to accumulate in granules. Assembly is driven by multivalent interactions among RNA-binding proteins with prion-like or low-complexity domains, notably G3BP1/2 and TIA-1/TIAR, among others. Disassembly follows stress relief and resumption of translation; chaperones and autophagic pathways can contribute to clearance.

Compositionally, stress granules contain mRNA, 40S ribosomal subunits, and initiation factors such as eIF3 and eIF4G, as well as RNA-binding proteins including G3BP1/2, TIA-1/TIAR, FMRP, YB-1, and DDX3X. They are distinct from processing bodies, though components can be exchanged between these granules. While stress granules primarily sequester mRNA and translation factors to pause translation, they are also thought to participate in RNA triage and signaling during cellular stress.

Clinical and research relevance is ongoing. Abnormal stress granule dynamics, persistent granules, or mutations in granule-associated proteins have been linked to neurodegenerative diseases such as ALS and frontotemporal dementia, highlighting their potential role in disease progression and as targets for therapeutic intervention.