negative regulation of stress granule assembly

Definition

Target type: biologicalprocess

Any process that stops or decreases the rate, frequency or extent of stress-granule assembly, the aggregation, arrangement and bonding together of proteins and RNA molecules to form a stress granule. [PMID:20180778]

Stress granules (SGs) are dynamic cytoplasmic assemblies that form in response to various cellular stresses, such as heat shock, oxidative stress, and viral infection. These granules sequester mRNAs and translation initiation factors, effectively halting protein synthesis and promoting cell survival. Negative regulation of SG assembly is crucial to maintain cellular homeostasis and prevent the accumulation of SGs under non-stressful conditions. Several mechanisms contribute to this regulation, including:

1. **Phosphorylation of SG components:** Key proteins involved in SG assembly, like TIA-1 and G3BP1, are regulated by phosphorylation. Kinases like AKT and MAPK can phosphorylate these proteins, inhibiting their ability to bind RNA and preventing SG formation.

2. **Protein degradation:** Ubiquitination and subsequent proteasomal degradation of SG components, like TIA-1 and RACK1, can reduce their abundance and suppress SG formation.

3. **Competition for binding sites:** Some proteins, like hnRNP A1, can compete with SG components for binding to specific mRNA sequences, thereby inhibiting their incorporation into SGs.

4. **Deadenylation of mRNA:** mRNAs targeted for SG sequestration often contain AU-rich elements (AREs) in their 3' UTR. Deadenylation of these mRNAs by deadenylases reduces their affinity for SG components, hindering their recruitment into SGs.

5. **Regulation of translation:** Factors that promote translation, like eIF4E and eIF4G, can compete with SG components for binding to mRNAs, preventing their sequestration into SGs.

6. **Chaperone activity:** Molecular chaperones, like HSP70 and HSP90, can interact with SG components and prevent their aggregation into SGs.

7. **Microenvironment changes:** Cellular stresses, such as heat shock, can alter the microenvironment within the cytoplasm, favoring the assembly of SGs. However, mechanisms like heat shock protein expression can counteract these changes, promoting SG disassembly.

8. **RNA binding proteins:** Specific RNA binding proteins, like HuR and AUF1, can bind to mRNAs and prevent their recruitment into SGs.

9. **Autophagy:** Autophagy can selectively target and degrade SGs, preventing their accumulation.

These mechanisms collectively ensure that SG assembly is tightly regulated, preventing their inappropriate formation and ensuring proper cellular function. Disturbances in these regulatory pathways can lead to aberrant SG assembly and contribute to disease pathogenesis.'
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Proteins (1)

Compounds (1)