Pharmacological activation of the Integrated Stress Response triggers a transcriptional program centered on ribosome biogenesis and function in honey bees

Seeking to further characterize the effect of Halofuginone in honey bees and to better understand cellular stress pathways in this species more generally, we used RNAseq to identify novel changes in gene expression after its ingestion and observed a striking induction of genes involved in ribosome biogenesis, translation, tRNA synthesis, and ribosome-associated quality control (RQC). Feeding bees cycloheximide (CHX) to halt ribosome translocation also induced all tested target genes, suggesting that this gene expression program could be induced by ribosome stalling in addition to tRNA-synthetase inhibition. Only a subset of these ribosome biogenesis genes are upregulated by UPR induction, suggesting that the ISR induces overlapping but distinct responses depending on the mode of activation and cross-talk with other cellular signaling pathways. Overall design: Six samples: 3 from honey bees fed Halofuginone, and 3 from honey bees fed DMSO (control).