Proteome diversification by adenosine to inosine RNA-editing

Nucleotide deamination is a widespread phenomenon frequently leading to a change of the genetic information. Adenosine deaminases that act on RNA (ADARs) convert adenosines to inosines in double-stranded or structured regions of RNAs. Inosines are interpreted as guanosines by most cellular processes and hence, this type of modification can affect the coding potential of an RNA but also its splicing, folding or stability, to name a few. While originally believed to be a rare event recent bioinformatic screens have demonstrated that RNA-editing by ADARs is widespread and very abundant in mammals. From these screens, editing sites were discovered in both coding and non-coding regions of mRNAs. In this review we focus on RNA-editing events that alter the coding potential of mRNAs and hence lead to the formation of proteins that differ from their genomically encoded versions. We will therefore discuss the role of ADARs in proteome diversification, in particular in the nervous system where editing is most abundant.