Related Experiment Video
Updated: Jun 22, 2025
Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
Published on: May 15, 2019
Stress granule-mediated sequestration of EGR1 mRNAs correlates with lomustine-induced cell death prevention
Marta Leśniczak-Staszak1, Paulina Pietras1, Marcin Ruciński1
1Department of Histology and Embryology, Poznan University of Medical Sciences, Poznań 60-781, Poland.
Abstract:
Some chemotherapy drugs modulate the formation of stress granules (SGs), which are RNA-containing cytoplasmic foci contributing to stress response pathways. How SGs mechanistically contribute to pro-survival or pro-apoptotic functions must be better defined. The chemotherapy drug lomustine promotes SG formation by activating the stress-sensing eIF2α kinase HRI (encoded by the EIF2AK1 gene). Here, we applied a DNA microarray-based transcriptome analysis to determine the genes modulated by lomustine-induced stress and suggest roles for SGs in this process. We found that the expression of the pro-apoptotic EGR1 gene was specifically regulated in cells upon lomustine treatment. The appearance of EGR1-encoding mRNA in SGs correlated with a decrease in EGR1 mRNA translation. Specifically, EGR1 mRNA was sequestered to SGs upon lomustine treatment, probably preventing its ribosome translation and consequently limiting the degree of apoptosis. Our data support the model where SGs can selectively sequester specific mRNAs in a stress-specific manner, modulate their availability for translation, and thus determine the fate of a stressed cell.
Insights
Chemotherapy drug lomustine induces stress granules (SGs), which sequester EGR1 mRNA. This sequestration limits translation, potentially reducing apoptosis and influencing cell fate during stress.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Stress granules (SGs) are cytoplasmic foci involved in cellular stress response pathways.
- The precise mechanisms by which SGs influence cell survival or apoptosis remain incompletely understood.
- Chemotherapy agents can modulate SG formation, impacting cellular responses to treatment.
Purpose of the Study:
- To investigate the role of stress granules in mediating cellular responses to the chemotherapy drug lomustine.
- To identify genes and pathways modulated by lomustine-induced stress and SG formation.
- To elucidate the mechanistic link between SG dynamics and gene expression during chemotherapy.
Main Methods:
- DNA microarray-based transcriptome analysis to identify lomustine-modulated genes.
- Analysis of stress granule (SG) formation and mRNA localization upon lomustine treatment.
- Assessment of mRNA translation efficiency for specific genes in the presence of SGs.
Main Results:
- Lomustine treatment induced stress granule (SG) formation via activation of the HRI kinase.
- The pro-apoptotic EGR1 gene expression was specifically regulated by lomustine.
- EGR1 mRNA was found sequestered within SGs, correlating with reduced translation and limited apoptosis.
Conclusions:
- Stress granules can selectively sequester specific mRNAs in a stress-dependent manner.
- SG sequestration of mRNA modulates its translational availability, influencing cell fate.
- This mechanism suggests a role for SGs in fine-tuning cellular responses to chemotherapy-induced stress.
Related Concept Videos
02:23Abnormal Proliferation
01:22MicroRNAs