RNA-specific adenosine deaminase (ADAR1, DSH, IFI4, p136, DRADA, DSRAD, K88dsRBP) mediates RNA editing by destabilizing double stranded RNA through deamination of adenosine to inosine in structured or double-stranded RNAs. ADAR1 is expressed from an interferon-response promoter and has a Z-DNA/Z-RNA binding domain at its N-terminus. ADAR1 co-localizes with SUMO-1 in a subnucleolar region that is distinct from the fibrillar center, the dense fibrillar component and the granular component. Localization of nuclear ADAR1 is under the influence of a nucleolar localization signal (NoLS) in the middle of ADAR1 and the exporting activity of the nuclear exporter signal (NES) near the N terminus. ADAR1 upregulates nuclear factor 90 (NF90)-mediated gene expression by interacting with NF110, NF90 and NF45. ADAR1 binds short interfering RNA (siRNA), and gene silencing by siRNA is significantly more effective in mouse fibroblasts homozygous for an ADAR1 null mutation than in wild-type cells. ADAR1 may limit the efficacy of siRNA in mammalian cells.
