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Stress granule-mediated sequestration of EGR1 mRNAs correlates with lomustine-induced cell death prevention

ABSTRACT: Some chemotherapy drugs influence the formation of stress granules (SGs), cytoplasmic RNA foci involved in stress response pathways. The exact role of SGs in promoting cell survival or apoptosis needs further clarification. The chemotherapy drug lomustine induces SG formation by activating the eIF2α kinase HRI (EIF2AK1). We performed a DNA microarray transcriptome analysis to identify genes affected by lomustine-induced stress and to explore the role of SGs. Our findings show that lomustine specifically regulates the expression of the pro-apoptotic EGR1 gene. The presence of EGR1 mRNA in SGs correlates with reduced translation of EGR1 mRNA. Lomustine likely sequesters EGR1 mRNA into SGs, preventing its ribosomal translation and thereby limiting apoptosis. This supports a model where SGs selectively sequester specific mRNAs in response to stress, modulate their translation, and thus determine the fate of stressed cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE269691 | GEO | 2024/06/20

REPOSITORIES: GEO

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