YB-1 recruitment to stress granules in zebrafish cells reveals a differential adaptive response to stress

Abstract

Abstract The survival of cells exposed to adverse environmental conditions entails various alterations in cellular function including major changes in the transcriptome as well as a radical reprogramming of protein translation. While in mammals this process has been extensively studied, stress responses in non-mammalian vertebrates remain poorly understood. One of the key cellular responses to many different types of stressors is the transient generation of structures called stress granules (SGs). These represent cytoplasmic foci where untranslated mRNAs are sorted or processed for re-initiation, degradation, or packaging into mRNPs. Here, using the evolutionarily conserved Y-box binding protein 1 (YB-1) and G3BP1 as markers, we have studied the formation of stress granules in zebrafish (D. rerio) in response to different environmental stressors. We show that following heat shock, zebrafish cells, like mammalian cells, form stress granules which contain both YB-1 and G3BP1 proteins. Moreover, zfYB-1 knockdown compromises cell viability, as well as recruitment of G3BP1 into SGs, under heat shock conditions highlighting the essential role played by YB-1 in SG assembly and cell survival. However, zebrafish PAC2 cells do not assemble YB-1-positive stress granules upon oxidative stress induced by arsenite, copper or hydrogen peroxide treatment. This contrasts with the situation in human cells where SG formation is robustly induced by exposure to oxidative stressors. Thus, our findings point to fundamental differences in the mechanisms whereby mammalian and zebrafish cells respond to oxidative stress.