Study of the interplay between Z-form dsRNA and ADAR1: revealing the mechanisms that prevent autoinflammatory disease and mapping their interaction at the molecular level.

ADAR1 binds RNA in the A-conformation (A-RNA) and the atypical Z-conformation (Z-RNA). Modification of endogenous A-RNA by ADAR1 inhibits unwanted activation of immune sensors. Whether ADAR1 additionally prevents erroneous detection of Z-RNA is unknown. We will study the molecular interplay between ADAR1 and Z-RNA and determine the consequences of disrupted interactions during the development of human autoimmune disease.