positive regulation of stress granule assembly

Definition

Target type: biologicalprocess

Any process that starts or increases 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, non-membrane bound cytoplasmic ribonucleoprotein (RNP) aggregates that form in response to various cellular stresses, such as heat shock, oxidative stress, nutrient deprivation, and viral infection. They serve as a crucial regulatory mechanism for cellular responses to stress by sequestering mRNAs and translation initiation factors, leading to a global translational repression. The assembly of SGs is a tightly regulated process involving a complex interplay of signaling pathways and protein-protein interactions. Positive regulation of SGs assembly involves a series of molecular events that promote the formation and growth of these aggregates. These events can be broadly categorized into:

**1. Stress-Induced Signal Transduction:**

- **Activation of Stress-Responsive Kinases:** Cellular stress triggers the activation of kinases, such as the eukaryotic initiation factor 2α kinase (eIF2αK) and the MAP kinases (MAPKs), which play a central role in SG assembly.
- **eIF2α Phosphorylation:** eIF2αK phosphorylates eIF2α, a key component of the translation initiation machinery, leading to its inactivation. This inhibition of translation initiation is a crucial event in SG formation.
- **MAPK Signaling:** MAPKs, activated by stress signals, regulate various cellular processes, including gene expression and protein synthesis. Their activation can directly or indirectly contribute to SG assembly.

**2. Recruitment of SG Components:**

- **mRNA Binding Proteins:** Stress-induced mRNA binding proteins, such as TIA-1, TIAR, G3BP1, and RBM4, play a central role in SG formation. These proteins recognize specific sequences within mRNAs and promote their sequestration into SGs.
- **Translation Initiation Factors:** eIF4E, eIF4G, and eIF3 are translation initiation factors that become incorporated into SGs during stress. Their sequestration contributes to the translational repression that characterizes SG assembly.
- **Other Proteins:** Other proteins involved in SG formation include the RNA helicase DDX6, the poly(A) binding protein PABP1, and the chaperone Hsp70. These proteins interact with mRNA binding proteins, translation factors, and other components of the SG machinery.

**3. Molecular Chaperones and Proteostasis:**

- **Hsp70 and Hsp90:** These chaperones are crucial for maintaining protein homeostasis and can assist in the formation and disassembly of SGs.
- **Ubiquitination and Proteasomal Degradation:** SGs are dynamic structures that can be disassembled under favorable conditions. Ubiquitination and proteasomal degradation play a role in removing components from SGs and restoring normal cellular function.

**4. Role of RNA Metabolism:**

- **mRNA Sequestration:** SGs function as repositories for specific mRNAs that are translationally repressed during stress. This sequestration can prevent the translation of potentially harmful proteins and promote cell survival.
- **RNA Binding Proteins:** SGs are enriched in RNA binding proteins that regulate RNA metabolism, including splicing, translation, and degradation.

**5. Feedback Regulation:**

- **Negative Feedback:** The assembly of SGs is often tightly regulated by negative feedback mechanisms. As SGs form, they can sequester components that are required for their own assembly, limiting their further growth.
- **Positive Feedback:** In some cases, the formation of SGs can trigger positive feedback loops that further enhance their assembly. This can be achieved through the activation of signaling pathways or the recruitment of additional components.

Overall, positive regulation of SG assembly is a complex process involving a delicate balance of signaling pathways, protein-protein interactions, and RNA metabolism. The formation of SGs is essential for cellular survival in response to stress, and their disruption can lead to various cellular dysfunctions and diseases.
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Proteins (1)

Compounds (11)