Stress granule-defective mutants deregulate stress responsive transcripts

Area of Science:

• Cell Biology
• Molecular Biology
• Genetics

Background:

• Eukaryotic cells form cytoplasmic aggregates called stress granules (SGs) to control gene expression under stress.
• The precise composition, assembly, and regulatory mechanisms of SGs are not fully understood.

Purpose of the Study:

• To identify genes involved in stress granule formation using a genome-wide screen in S. cerevisiae.
• To investigate the role of SGs in cellular stress response pathways.

Main Methods:

• Genome-wide screen of S. cerevisiae gene deletion mutants for defects in SG formation during glucose starvation.
• Analysis of SG-defective mutants under various stress conditions.
• Investigation of proteins associated with SG defects and their structural properties.
• Assessment of heat-induced mutation rates in SG-defective mutants.
• Examination of transcript levels in SG-defective mutants.

Main Results:

• Identified numerous genes, many previously unlinked to SGs, that are crucial for SG formation.
• Discovered that some SG defects are stress-specific, while others are general.
• Found that proteins involved in SG defects are enriched in low-complexity regions, suggesting weak interactions maintain SG structure.
• Observed that certain SG-defective mutants exhibit increased heat-induced mutation rates.
• Demonstrated that mutations affecting Ran GTPase impact SG formation.
• Showed that stress-induced mRNAs accumulate and stress-repressed mRNAs decrease further in cells lacking SGs.

Conclusions:

• Stress granules play a regulatory role in cellular stress responses, not just being a consequence of stress.
• SGs modulate the extent of cellular reactions to stress, preventing excessive responses.
• Nucleocytoplasmic transport of RNA-binding proteins, modulated by SGs, is likely essential for stress-induced gene expression regulation.