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(1) Background: The Gagr gene in Drosophila melanogaster’s genome originated from the molecular domestication of retrotransposons and retroviruses’ gag gene. In all Drosophila species, the Gagr protein homologs exhibit a conserved structure, indicative of a vital role. Previous studies have suggested a potential link between the Gagr gene function and stress responses. (2) Methods: We compared flies with Gagr gene knockdown in all tissues to control flies in physiological tests and RNA-sequencing experiments. (3) Results: Flies with the Gagr gene knockdown exhibited shorter lifespans compared to control flies. Transcriptome analysis revealed that Gagr knockdown flies showed elevated transcription levels of immune response genes. We used ammonium persulfate, a potent stress inducer, to elicit a stress response. In control flies, ammonium persulfate activated the Toll, JAK/STAT, and JNK/MAPK signaling pathways. In contrast, flies with the Gagr gene knockdown displayed reduced expression of stress response genes. Gene ontology enrichment analysis identified categories of genes upregulated under ammonium persulfate stress in control flies but not in Gagr knockdown flies. These genes are involved in developmental control, morphogenesis, and central nervous system function. (4) Conclusion: Our findings indicate the significance of the Gagr gene in maintaining immune response and homeostasis.

The prevention of muscle atrophy carries with it clinical significance for the control of increased morbidity and mortality following physical inactivity. While major transcriptional events associated with muscle atrophy-recovery processes are the subject of active research on the gene level, the contribution of non-coding regulatory elements and alternative promoter usage is a major source for both the production of alternative protein products and new insights into the activity of transcription factors. We used the cap-analysis of gene expression (CAGE) to create a genome-wide atlas of promoter-level transcription in fast (m. EDL) and slow (m. soleus) muscles in rats that were subjected to hindlimb unloading and subsequent recovery. We found that the genetic regulation of the atrophy-recovery cycle in two types of muscle is mediated by different pathways, including a unique set of non-coding transcribed regulatory elements. We showed that the activation of “shadow” enhancers is tightly linked to specific stages of atrophy and recovery dynamics, with the largest number of specific regulatory elements being transcriptionally active in the muscles on the first day of recovery after a week of disuse. The developed comprehensive database of transcription of regulatory elements will further stimulate research on the gene regulation of muscle homeostasis in mammals.