One hundred million adenosine-to-inosine RNA editing sites: hearing through the noise

The most recent work toward compiling a comprehensive database of adenosine-to-inosine RNA editing events suggests that the potential for RNA editing is much more pervasive than previously thought; indeed, it is manifest in more than 100 million potential editing events located primarily within Alu repeat elements of the human transcriptome. Pairs of inverted Alu repeats are found in a substantial number of human genes, and when transcribed, they form long double-stranded RNA structures that serve as optimal substrates for RNA editing enzymes. A small subset of edited Alu elements has been shown to exhibit diverse functional roles in the regulation of alternative splicing, miRNA repression, and cis-regulation of distant RNA editing sites. The low level of editing for the remaining majority may be non-functional, yet their persistence in the primate genome provides enhanced genomic flexibility that may be required for adaptive evolution.