10.3389/fpsyt.2019.00277.s002
Alec L. W. Dick
Alec L. W.
Dick
Khen Khermesh
Khen
Khermesh
Evan Paul
Evan
Paul
Fabian Stamp
Fabian
Stamp
Erez Y. Levanon
Erez Y.
Levanon
Alon Chen
Alon
Chen
Table_2_Adenosine-to-Inosine RNA Editing Within Corticolimbic Brain Regions Is Regulated in Response to Chronic Social Defeat Stress in Mice.xlsx
Frontiers
2019
A-to-I RNA editing
chronic social defeat stress
microfluidics-based multiplex polymerase chain reaction
adenosine deaminases acting on RNA
ADAR
chronic stress
2019-05-06 14:01:49
Dataset
https://frontiersin.figshare.com/articles/dataset/Table_2_Adenosine-to-Inosine_RNA_Editing_Within_Corticolimbic_Brain_Regions_Is_Regulated_in_Response_to_Chronic_Social_Defeat_Stress_in_Mice_xlsx/8082590
<p>Adenosine-to-inosine (A-to-I) RNA editing is a co-/posttranscriptional modification of double-stranded RNA, catalyzed by the adenosine deaminase acting on RNA (ADAR) family of enzymes, which results in recognition of inosine as guanosine by translational and splicing machinery causing potential recoding events in amino acid sequences. A-to-I editing is prominent within brain-specific transcripts, and dysregulation of editing at several well-studied loci (e.g., Gria2, Htr2c) has been implicated in acute and chronic stress in rodents as well as neurological (e.g., Alzheimer’s) and psychopathological disorders such as schizophrenia and major depressive disorder. However, only a small fraction of recoding sites has been investigated within the brain following stress, and our understanding of the role of RNA editing in transcriptome regulation following environmental stimuli remains poorly understood. Thus, we aimed to investigate A-to-I editing at hundreds of loci following chronic social defeat stress (CSDS) in mice within corticolimbic regions responsive to chronic stress regulation. Adult male mice were subjected to CSDS or control conditions for 21 days and dynamic regulation of A-to-I editing was investigated 2 and 8 days following the final defeat within both the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA). Employing a targeted resequencing approach, which utilizes microfluidics-based multiplex polymerase chain reaction (PCR) coupled with next-generation sequencing, we analyzed A-to-I editing at ∼100 high-confidence editing sites within the mouse brain. CSDS resulted in acute regulation of transcripts encoding several ADAR enzymes, which normalized 8 days following the final defeat and was specific for susceptible mice. In contrast, sequencing analysis revealed modest and dynamic regulation of A-to-I editing within numerous transcripts in both the mPFC and BLA of resilient and susceptible mice at both 2 and 8 days following CSDS with minimal overlap between regions and time points. Editing within the Htr2c transcript and relative abundance of Htr2c messenger RNA (mRNA)variants were also observed within the BLA of susceptible mice 2 days following CSDS. These results indicate dynamic RNA editing within discrete brain regions following CSDS in mice, further implicating A-to-I editing as a stress-sensitive molecular mechanism within the brain of potential relevance to resiliency and susceptibility to CSDS.</p>