Abstract
Emerging evidence suggests that RNA editing is associated with stress, neurological diseases, and psychiatric disorders. However, the role of G-to-A RNA editing in chronic social defeat stress (CSDS) remains unclear. We herein identified G-to-A RNA editing and its changes in the ventral tegmental area (VTA), a key region of the brain reward system, in CSDS mouse models under emotional stress (ES) and physiological stress (PS) conditions. Our results revealed 3812 high-confidence G-to-A editing events. Among them, 56 events were significantly downregulated while 23 significantly upregulated in CSDS compared to controls. Moreover, divergent editing patterns were observed between CSDS mice under ES and PS conditions, with 42 and 21 events significantly upregulated in PS and ES, respectively. Interestingly, differential RNA editing was enriched in genes with multiple editing events. Genes differentially edited in CSDS included those genetically associated with mental or neurodevelopmental disorders, especially mood disorders, such as FAT atypical cadherin 1 and solute carrier family 6 member 1. Notably, changes of G-to-A RNA editing were also implicated in ionotropic glutamate receptors, a group of well-known targets of adenosine-to-inosine RNA editing. Such results demonstrate dynamic G-to-A RNA editing changes in the brain of CSDS mouse models, underlining its role as a potential molecular mechanism of CSDS and stress-related diseases.
Highlights
RNA editing is the change of RNA nucleotide sequence that occurs at the transcriptional level (Tan et al, 2017)
The rodent model of chronic social defeat stress (CSDS) has been widely used in the study of stress-related diseases such as major depression and posttraumatic stress disorder (PTSD), providing an important and useful tool for the understanding of these diseases
The current study for the first time systematically investigated G-to-A RNA editing in the brain ventral tegmental area (VTA) in CSDS mice at the transcriptome-level, and demonstrated dynamic changes of G-to-A RNA editing associated with CSDS as well as divergent editing patterns found under emotional stress (ES) or physiological stress (PS) conditions
Summary
RNA editing is the change of RNA nucleotide sequence that occurs at the transcriptional level (Tan et al, 2017). RNA editing has been found in various organisms, including animals (Tan et al, 2017), plants (Small et al, 2020), and humans. G-to-A RNA Editing in Stress (Christofi and Zaravinos, 2019), and is involved in a variety of physiological and pathological processes. Recent studies have suggested that RNA editing significantly changes in response to stress, neurological diseases and psychiatric disorders (Kawahara et al, 2004; Breen et al, 2019; Dick et al, 2019), suggesting that it may be involved in the molecular mechanisms of these pathological processes. The role of G-to-A editing in physiological and pathological processes is largely unclear
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