A-to-I RNA editing prevents an inflammation-mediated lipodystrophy in adipose tissue

RNA editing is a post-transcriptional mechanism that alters the specific nucleotide sequences of RNA to enhance the diversity of gene products. However, the biological function of RNA-editing in different cell types remained poorly understood. In this study, we delineated a comprehensive RNA editome across brown, visceral and subcutaneous adipose tissues from both human and mouse. The edited genes in two species are significantly overlapped and highly enriched for RNA metabolism and lipid metabolism pathways. Using an adipose tissue-specific Adar1 knockout mouse model, we demonstrated that the deficiency of A-to-I editing, through an enhanced formation of double strand RNA (dsRNA) structures, resulted in an inflammation-mediated lipodystrophy which can be fully rescued by deleting Ifih1, a sensor for dsRNA structures. Taken together, our study has addressed a new and fundamental question about the function of RNA editing in adipose tissue.