Dynamic Dysregulation of Ribosomal Protein Genes in Mouse Brain Stress Models

Emphasizing their evolutionarily conserved role in stress adaptation mechanisms, ribosomal protein genes (RPGs) are observed to be downregulated in various stressors and across phyla. However, this evolutionarily conserved stress response is not well explored in mouse models of neurobiological stress. This study investigates the dysregulation patterns of RPGs in various murine preclinical stress paradigms across different brain regions using available transcriptomic data and identifies the non-canonical ribosomal functions using synaptic gene-ontology terms. Without a discernible structure across different brain areas, we observed heterogeneous dysregulation, encompassing either up or downregulation in both cytoplasmic and mitochondrial RPGs. However, downregulation was more prominent than upregulation, and the overall dysregulation seems more prevalent in the chronic stress paradigm compared to stress paradigms involving acute and early-life stress. Enrichment analysis significantly associates dysregulated RPGs with post-synaptic gene ontology terms, emphasizing their involvement in synaptic modulation. Overall, the study demonstrates ribosomal dysregulation as an evolutionarily conserved stress response mechanism during different mouse stress paradigms. We discuss the possibility that the variability in the directionality of dysregulation may emerge as a potential marker of neuronal activity in response to diverse stress paradigms and the involvement of paradigm-specific RPG dysregulation either in the process of global downscaling of ribosome biogenesis or in the process of ribosomal heterogeneity, each leading to a different effect.