Editome profiling and cross-cohort validation reveal A-to-I RNA editing dysregulation in the hippocampus and prefrontal cortex of sepsis patients.

Introduction: Sepsis is a severe systemic inflammatory response to infection, potentially resulting in serious neurological complications. Adenosine-to-inosine (A-to-I) RNA editing is a critical epitranscriptomic process, yet its clinical involvement in different brain regions during sepsis remains to be elucidated. Methods: We conducted a comprehensive editome analysis and experimental validation to characterize A-to-I RNA editing in hippocampal and prefrontal cortical tissues from a sepsis cohort, as well as in brain tissues from a validation cohort. Results: Our findings revealed diverse dysregulation of RNA editing in these brain regions, with a substantial reduction in average RNA editing levels in the hippocampus but not in the prefrontal cortex. Moreover, cross-cohort and cross-tissue analysis identified eight key genes with dysregulated RNA editing during sepsis, particularly mitochondrial antiviral-signaling protein ( Discussion: Our results thus provide new insight into the importance of the clinical epitranscriptomic landscape in different brain regions during sepsis and warrant further investigation into therapeutic strategies to mitigate cognitive impairment in sepsis.