Adenosine deaminases acting on RNA (ADARs) are zinc-containing enzymes that deaminate adenosine bases to inosines within dsRNA regions in transcripts. In short, structured dsRNA hairpins individual adenosine bases may be targeted specifically and edited with up to one hundred percent efficiency, leading to the production of alternative protein variants. However, the majority of editing events occur within longer stretches of dsRNA formed by pairing of repetitive sequences. Here, many different adenosine bases are potential targets but editing efficiency is usually much lower. Recent work shows that ADAR-mediated RNA editing is also required to prevent aberrant activation of antiviral innate immune sensors that detect viral dsRNA in the cytoplasm. Missense mutations in the ADAR1 RNA editing enzyme cause a fatal auto-inflammatory disease, Aicardi-Goutières syndrome (AGS) in affected children. In addition RNA editing by ADARs has been observed to increase in many cancers and also can contribute to vascular disease. Thus the role of RNA editing in the progression of various diseases can no longer be ignored. The ability of ADARs to alter the sequence of RNAs has also been used to artificially target model RNAs in vitro and in cells for RNA editing. Potentially this approach may be used to repair genetic defects and to alter genetic information at the RNA level. In this review we focus on the role of ADARs in disease development and progression and on their potential use to artificially modify RNAs in a targeted manner.

• Keywords
• Adenosine deaminases acting on RNA, Aicardi Guitieres Syndrome, RNA-editing, self versus non-self, target editing,
• MeSH
• Adenosine Deaminase metabolism   MeSH
• RNA Editing * MeSH
• Immunity MeSH
• Humans MeSH
• Disease Susceptibility * MeSH
• Mammals MeSH
• RNA Stability MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Adenosine Deaminase MeSH

Our knowledge of the variety and abundances of RNA base modifications is rapidly increasing. Modified bases have critical roles in tRNAs, rRNAs, translation, splicing, RNA interference, and other RNA processes, and are now increasingly detected in all types of transcripts. Can new biological principles associated with this diversity of RNA modifications, particularly in mRNAs and long non-coding RNAs, be identified? This review will explore this question by focusing primarily on adenosine to inosine (A-to-I) RNA editing by the adenine deaminase acting on RNA (ADAR) enzymes that have been intensively studied for the past 20 years and have a wide range of effects. Over 100 million adenosine to inosine editing sites have been identified in the human transcriptome, mostly in embedded Alu sequences that form potentially innate immune-stimulating dsRNA hairpins in transcripts. Recent research has demonstrated that inosine in the epitranscriptome and ADAR1 protein establish innate immune tolerance for host dsRNA formed by endogenous sequences. Innate immune sensors that detect viral nucleic acids are among the readers of epitranscriptome RNA modifications, though this does preclude a wide range of other modification effects.

• MeSH
• Adenosine genetics   MeSH
• Adenosine Deaminase genetics   MeSH
• Aminohydrolases genetics   MeSH
• RNA Editing genetics   MeSH
• Inosine genetics   MeSH
• Humans MeSH
• RNA, Messenger genetics   MeSH
• RNA Processing, Post-Transcriptional genetics   MeSH
• Immunity, Innate genetics   MeSH
• RNA-Binding Proteins genetics   MeSH
• Transcriptome genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• ADAR protein, human MeSH Browser
• adenine deaminase MeSH Browser
• Adenosine MeSH
• Adenosine Deaminase MeSH
• Aminohydrolases MeSH
• Inosine MeSH
• RNA, Messenger MeSH
• RNA-Binding Proteins MeSH