Stress granules

What are stress granules?

Stress granules are membrane-free structures formed through condensation. This process happens in the cytoplasm in response to stressful environmental stimuli, such as oxidative stress, heat shock, hypoxia, mitochondrial stress, UV radiation, bacterial or viral infections and osmotic shock. Stress granules are described as dynamic structures containing accompanying substructures.

The composition of stress granules

Stress granules contain multiple hundreds of protein and RNA molecules. They also contain 40S ribosome subunits, poly(A) mRNA and RNA-binding proteins. Given that they can also contain components necessary to initiate translation, it has been hypothesized that stress granules develop as storage for RNA molecules. It has also been discovered that mRNA translation can happen in stress granules. The key molecule in stress granules is RNA. An increase in the concentration of mRNA free from ribosomes has been connected to the formation of stress granules during stress. The kind of protein that will participate in the formation of stress granules depends on the kind of cell in which they are formed, as well as the form of stress the cell is enduring.

The role of stress granules

Stress granules are key to cell survival due to their role in regulating translation, storage of mRNA and other biomolecules, as well as stabilization and cell signalization during oxidative stress. They regulate gene expression and prohibit viral replication. mRNA molecules stored in stress granules in the form of messenger ribonucleoproteins (mRNP) exhibit inhibited function and translation, which preserves energy needed by other cell components responding to stress. Stress granules are temporary structures which break down once the stressor is removed. If the stress is too overwhelming for the cell, stress granules do not break down and instead become permanent. In that case, the cell does not undergo repair processes. Instead, it enters apoptosis – programmed cell death.

Stress granules and disease

RBP containing stress granules are key to regulating the expression of neuronal genes. Stress granules are formed simultaneously with pathological protein aggregates. These aggregates are often related to neurodegenerative diseases such as amyotrophic lateral sclerosis and Alzheimer’s disease, as well as polyglutamine diseases in which insoluble aggregates are formed. Mutations that lead to changes in the formation of stress granules can also lead to the development of some neurodegenerative diseases and some forms of carcinoma. Many studies focus on stress granules since their pathological aggregation is being explored as analogous to the aggregation of pathogenetic proteins in degenerative diseases.