adenosinetoinosine

Adenosine-to-inosine editing, or A-to-I editing, is a post-transcriptional modification in which adenosine residues within double-stranded RNA are deaminated to inosine by enzymes of the adenosine deaminase acting on RNA (ADAR) family. Inosine is interpreted as guanosine by the cellular machinery, leading to potential changes in the encoded protein, RNA stability, splicing, or microRNA processing.

Three mammalian ADAR enzymes are known: ADAR1, ADAR2, and ADAR3, with ADAR1 and ADAR2 displaying catalytic activity. Editing commonly occurs in noncoding regions but has notable coding-site effects, such as the Q/R site in the GRIA2 subunit of the AMPA receptor, which is essential for proper calcium permeability. Many other substrates include transcripts for potassium channels and serotonin receptors.

Biological impact: A-to-I editing diversifies the transcriptome without altering the underlying genome. It is developmentally regulated and enriched in the brain. Inosine is read as guanosine by ribosomes and spliceosomal machinery, so editing can recode amino acids, alter splicing, or affect transcript stability. Aberrant editing is associated with neurological disorders, epilepsy, psychiatric conditions, and cancer. High-throughput sequencing reveals thousands of editing sites, most tissue-specific and of unclear function; editing levels can vary with development, cellular context, and immune signaling.