Site-selective versus promiscuous A-to-I editing

RNA editing by adenosine deamination is acting on polymerase II derived transcripts in all metazoans. Adenosine-to-inosine (A-to-I) editing is mediated by the adenosine deaminase that acts on RNA (ADAR) enzymes. Two types of adenosine to inosine (A-to-I) RNA editing have been defined: site selective and hyper-editing. Typically, in site selectively edited substrates, one or a few A-to-I sites are edited in double-stranded RNA structures, frequently interrupted by single-stranded bulges and loops. Hyper-editing occurs in long stretches of duplex RNA where multiple adenosines are subjected to deamination. In this review, recent findings on editing within noncoding RNA as well as examples of site selective editing within coding regions are presented. We discuss how these two editing events have evolved and the structural differences between a site selective and hyper-edited substrate.