Adenosine deaminase acting on RNA (ADAR1), a suppressor of double-stranded RNA-triggered innate immune responses

J Biol Chem. 2019 Feb 1;294(5):1710-1720. doi: 10.1074/jbc.TM118.004166.

Abstract

Herbert "Herb" Tabor, who celebrated his 100th birthday this past year, served the Journal of Biological Chemistry as a member of the Editorial Board beginning in 1961, as an Associate Editor, and as Editor-in-Chief for 40 years, from 1971 until 2010. Among the many discoveries in biological chemistry during this period was the identification of RNA modification by C6 deamination of adenosine (A) to produce inosine (I) in double-stranded (ds) RNA. This posttranscriptional RNA modification by adenosine deamination, known as A-to-I RNA editing, diversifies the transcriptome and modulates the innate immune interferon response. A-to-I editing is catalyzed by a family of enzymes, adenosine deaminases acting on dsRNA (ADARs). The roles of A-to-I editing are varied and include effects on mRNA translation, pre-mRNA splicing, and micro-RNA silencing. Suppression of dsRNA-triggered induction and action of interferon, the cornerstone of innate immunity, has emerged as a key function of ADAR1 editing of self (cellular) and nonself (viral) dsRNAs. A-to-I modification of RNA is essential for the normal regulation of cellular processes. Dysregulation of A-to-I editing by ADAR1 can have profound consequences, ranging from effects on cell growth and development to autoimmune disorders.

Keywords: 2'-5'-oligoadenylate synthetase; ADAR; RIG-I–like receptor (RLR); RNA deamination; RNA editing; adenosine deaminase acting on RNA; double-stranded RNA (dsRNA); innate immunity; interferon; protein kinase PKR.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adenosine Deaminase / metabolism*
  • Humans
  • Immunity, Innate / immunology*
  • Immunity, Innate / physiology
  • RNA, Double-Stranded / metabolism*
  • RNA-Binding Proteins / metabolism*

Substances

  • RNA, Double-Stranded
  • RNA-Binding Proteins
  • ADAR protein, human
  • Adenosine Deaminase