Dissecting independent functions of the RNA editing enzyme ADAR1 in health and disease

Abstract

ADAR1 is an enzyme that edits adenosine to inosine (A-to-I editing) in double-stranded RNA (dsRNA) from both endogenous and viral sources. This editing can alter RNA sequence, stability, and structure. ADAR1 exists in two isoforms: ADAR1p150 (p150), which is cytoplasmic and inducible by interferon or viral infection, and ADAR1p110 (p110), which is constitutively expressed in the nucleus and nucleolus. Mouse genetics demonstrated that ADAR1-mediated editing of endogenous dsRNA is essential for normal development by inhibiting MDA5/MAVS mediated innate immune activation. The protein-dependent but editing-independent functions of ADAR1 are also critical for postnatal survival of mice, attribute..