Stress granule-mediated sequestration of EGR1 mRNAs correlates with lomustine-induced cell death prevention.
Marta Leśniczak-StaszakPaulina PietrasMarcin RucińskiRyan JohnstonMateusz SowińskiMałgorzata AndrzejewskaMichał NowickiEwelina GowinShawn M LyonsPavel IvanovWitold SzaflarskiPublished in: Journal of cell science (2024)
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.
Keyphrases
- cell death
- cell cycle arrest
- anti inflammatory
- stress induced
- drug induced
- binding protein
- poor prognosis
- genome wide analysis
- transcription factor
- induced apoptosis
- signaling pathway
- locally advanced
- single cell
- machine learning
- endoplasmic reticulum stress
- cell proliferation
- cell therapy
- bone marrow
- tyrosine kinase
- pi k akt
- radiation therapy
- artificial intelligence
- deep learning
- free survival
- protein kinase