In cellular biology, stress granules are biomolecular condensates in the cytosol composed of proteins and RNAs that assemble into 0.1–2 μm membraneless organelles when the cell is under stress. The mRNA molecules found in stress granules are stalled translation pre-initiation complexes associated with 40S ribosomal subunits, translation initiation factors, poly(A)+ mRNAs and RNA-binding proteins (RBPs). While they are membraneless organelles, stress granules have been proposed to be associated with the endoplasmatic reticulum. There are also nuclear stress granules. This article is about the cytosolic variety.
Proposed functions
The function of stress granules remains largely unknown. Stress granules have long been proposed to have a function to protect RNAs from harmful conditions, thus their appearance under stress. The accumulation of RNAs into dense globules could keep them from reacting with harmful chemicals and safeguard the information coded in their RNA sequence.
Stress granules might also function as a decision point for untranslated mRNAs. Molecules can go down one of three paths: further storage, degradation, or re-initiation of translation. Conversely, it has also been argued that stress granules are not important sites for mRNA storage nor do they serve as an intermediate location for mRNAs in transit between a state of storage and a state of degradation.
Efforts to identify all RNAs within stress granules (the stress granule transcriptome) in an unbiased way by sequencing RNA from biochemically purified stress granule "cores" have shown that RNAs are not recruited to stress granules in a sequence-specific manner, but rather generically, with longer and/or less-optimally translated transcripts being enriched. These data imply that the stress granule transcriptome is influenced by the valency of RNA (for proteins or other RNAs) and by the rates of RNA run-off from polysomes. The latter is further supported by recent single molecule imaging studies. Furthermore, it was estimated that only about 15% of the total mRNA in the cell is localized to stress granules, suggesting that stress granules only influence a minority of mRNAs in the cell and may not be as important for mRNA processing as previously thought. That said, these studies represent only a snapshot in time, and it is likely that a larger fraction of mRNAs are at one point stored in stress granules due to those RNAs transiting in and out.
The stress proteins that are the main component of stress granules in plant cells are molecular chaperones that sequester, protect, and possibly repair proteins that unfold during heat and other types of stress. Therefore, any association of mRNAs with stress granules may simply be a side effect of the association of partially unfolded RNA-binding proteins with stress granules, similar to the association of mRNAs with proteasomes.
Formation
Environmental stressors trigger cellular signaling, eventually leading to the formation of stress granules. In vitro, these stressors can include heat, cold, oxidative stress (sodium arsenite), endoplasmic reticulum stress (thapsigargin), proteasome inhibition (MG132), hyperosmotic stress, ultraviolet radiation, inhibition of eIF4A (pateamine A, hippuristanol, or RocA), nitric oxide accumulation after treatment with 3-morpholinosydnonimine (SIN-1), perturbation of pre-mRNA splicing, and other stressors, like puromycin, which result in disassembled polysomes. Many of these stressors result in the activation of particular stress-associated kinases (HRI, PERK, PKR, and GCN2), translational inhibition and stress granule formation. Stress granules will also form upon Gαq activation in a mechanism that involves the release of stress granule associated proteins from the cytosolic population of the Gαq effector phospholipase Cβ.