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The decision-making hub of translation: What role do stress granules play in mRNA fate?
In cell biology, stress granules are biomolecular condensates composed of proteins and RNA. When cells experience stress, they assemble into 0.1 to 2 micron membraneless organelles in the cytoplasm. The mRNA molecules contained in these stress granules originate from stalled pre-translational initiation complexes associated with the 40S ribosomal subunit, translation initiation factors, polyA+ mRNA, and RNA-binding proteins (RBPs). Although they are membraneless organelles, some studies have suggested that stress granules may be associated with the endoplasmic reticulum. In addition, nuclear stress granules are present, but this article will focus on stress granules in the cytoplasm.
The primary function of stress granules is still not widely understood, however some studies suggest that they may function to protect RNA so that it is not damaged under harmful conditions.
Formation of pressure particles
Environmental stressors trigger cellular signals that ultimately lead to the formation of stress granules. In in vitro experiments, these stressors can include high temperature, low temperature, oxidative stress, and inhibition of translation. What these stressors have in common is that they activate specific stress-related kinases, ultimately leading to translational inhibition and the formation of stress granules. For example, stress granules are also formed upon Gαq activation, a process that involves the release of stress granule-associated proteins from the cytoplasm.
Many signaling molecules have also been shown to regulate the formation or dynamics of stress granules, including AMP kinase, known as an "energy sensor."
Potential role of RNA-RNA interaction
RNA phase transitions are driven in part by intermolecular RNA-RNA interactions, which may play a role in the formation of stress granules. Several enzymes, including RNA helicases, are found in stress granules and may influence the dynamics of these granules. Recent studies have shown that RNA in stress granules is more compact than RNA in the cytoplasm and may undergo post-translational modifications.
Some scholars speculate that RNA aggregation and RNA-RNA interaction play an important role in the formation of stress granules, and this process may be regulated by RNA helicase.
Relationship between pressure particles and treatment bodies
Stress granules share many features with processing bodies, including sharing certain RNA and protein components, co-occurring under stress, and may be physically associated with each other. Although they influence each other in some ways, the two are not functionally identical. Stress granules are considered to be the storage sites of mRNA, while processing bodies are related to the mRNA degradation process. This dividing line is not clear, and there is evidence that processing bodies may be precursors that promote pressure granule formation.
Although certain protein components are shared between stress granules and processing bodies, their protein combinations are largely unique.
Future research directions
Despite recent progress in research on stress granules, their complete proteome is still not fully understood. Researchers are working on a more comprehensive study of pressure particles through different techniques to understand their complete composition and function. Future studies may reveal the specific roles of these cellular structures in regulating mRNA fate and provide new insights into disease treatment.
The function and mechanism of pressure granules are still hot issues in the biological world. When we deeply explore their formation and functions, will we gain a deeper understanding of the basic operation of life?
