Cellular Self-RNA Triggers Inflammation

Presenter: Dr. Qingde Wang

Dr. Wang's research focuses on the study of cellular RNA editing and RNA signaling, and in particular on the RNA editing enzyme ADAR1 and how it regulates RNA sensing signaling pathways involved in innate immunity. Dr. Wang's research has made significant contributions to understanding the function and mechanism of cellular RNA processes, and to the related signaling pathways in physiologic and pathologic conditions. He was the first to generate an ADAR1 knockout mouse model and demonstrated an essential role of this RNA editing enzyme in mouse embryo development. Taking advantage of inducible KO mouse models and the derived primary cells, Dr. Wang's lab first discovered that ADAR1 regulates the innate immune response through cytosolic RNA receptors. Cellular RNAs activate the RNA sensing pathway when ADAR1 is absent, however, cellular RNAs edited by ADAR1 prevent activation of the RNA sensing signaling pathway. Through collaborations, Dr. Wang has investigated the function of ADAR1 in tissue inflammatory injuries, as demonstrated in the liver. Through generation of a series of cell type specific KO mouse models, he demonstrated a significant role of RNA editing in inflammatory tissue injury induced by sterile inflammatory processes, and recent studies found that lipid metabolic stress suppresses ADAR1 expression in both humans and mice. These findings strongly indicate a potential role of RNA editing in metabolic diseases, although how endogenous cellular RNAs activate cytosolic RNA sensing signaling pathways and how this is regulated by RNA editing remains largely unknown. RNA editing is likely at the crux of the metabolic stress, cellular RNA process and inflammatory tissue injuries.

Background references:

• RNA Editing, ADAR1, and the Innate Immune Response
• Adenosine deaminase acting on RNA 1 limits RIG-I RNA detection and suppresses IFN production responding to viral and endogenous RNAs
• ADAR1 Suppresses the Activation of Cytosolic RNA-Sensing Signaling Pathways to Protect the Liver from Ischemia/Reperfusion Injury