RNA rewriting, recoding, and rewiring in human disease

•A-to-I editing increases transcriptome diversity through multiple mechanisms.•Aberrant regulation of A-to-I editing promotes cancer and degenerative disease.•The functional impact of many RNA editing sites is still not fully understood.•Treatments reverting A-to-I editing may have great potential in several diseases.

ADAR (adenosine deAminase acting on RNA) editases catalyze the deamination of adenosine to inosine (A-to-I), a post-transcriptional modification that alters coding and non-coding RNA stability and function. ADAR editases such as ADAR1 have recently been shown to play a key role in normal stem cell maintenance. While ADAR mutations are associated with hereditary autoimmune diseases such as Aicardi–Goutières syndrome, ADAR copy-number alterations and editase activation have been associated with progression of a broad array of malignancies. In this review we discuss evidence linking aberrant A-to-I editing to cancer and other degenerative diseases, and the mechanisms that may be targeted by novel therapeutic strategies.