Adenosine Deaminases Acting on RNA (ADARs) and Viral Infections

C6 deamination of adenosine (A) to inosine (I) in double-stranded RNA (dsRNA) is catalyzed by a family of enzymes known as ADARs (adenosine deaminases acting on RNA) encoded by three genes in mammals. Alternative promoters and splicing produce two ADAR1 proteins, an interferon-inducible cytoplasmic p150 and a constitutively expressed p110 that like ADAR2 is a nuclear enzyme. ADAR3 lacks deaminase activity. A-to-I editing occurs with both viral and cellular RNAs. Deamination activity is dependent on dsRNA substrate structure and regulatory RNA-binding proteins and ranges from highly site selective with hepatitis D RNA and glutamate receptor precursor messenger RNA (pre-mRNA) to hyperediting of measles virus and polyomavirus transcripts and cellular inverted Alu elements. Because I base-pairs as guanosine instead of A, editing can alter mRNA decoding, pre-mRNA splicing, and microRNA silencing. Editing also alters dsRNA structure, thereby suppressing innate immune responses including interferon production and action.

Automated summary

C6 deamination of adenosine to inosine in dsRNA is catalyzed by ADARs enzymes encoded by three genes in mammals. Different ADAR1 proteins, p150 and p110, are produced through alternative promoters and splicing, with ADAR2 being a nuclear enzyme. A-to-I editing occurs in both viral and cellular RNAs, with activity dependent on substrate structure and regulatory RNA-binding proteins.