SINEs point to abundant editing in the human genome

Many double-stranded RNAs (dsRNAs) in cells, especially those in the nucleus, are susceptible to base editing in which adenosines are deaminated to inosines by enzymes known as dsRNA-specific adenosine deaminases (ADARs) [1]. This editing leads to a recoding of the genetic information, because inosines are translated as if they were guanosines. Thus, RNA editing can have dramatic consequences for the expression of genetic information, and in a number of cases it has been shown to lead to the expression of proteins not only with altered amino-acid sequences from those predicted from the DNA sequence, but also with altered biological functions [1,2].It seems there are two types of RNA editing, selective and promiscuous. Selective editing (Figure 1a) results in the conversion of one or a few adenosines in a transcript to inosines; it is generally associated with the expression of proteins with altered functions. These editing events usually occur within relatively short and incompletely base-paired sequences that form between the edited exon and a nearby intron, and they are directed to specific adenosine residues (for example, see [2]). Promiscuous editing, on the other hand, involves the deamination of numerous adenosines in RNA duplexes that are generally longer than 30 base-pairs (bp; Figure 1b) [1]. This type of editing is thought to be the result of aberrant production of dsRNA and has been suggested to lead to RNA degradation [3], nuclear retention [4] or even gene silencing [5].In the past several years, interest in the prevalence of editing in the human genome and in the identity of endogenous editing substrates has grown. Recent work using computational approaches has provided intriguing and unexpected results. Independently and almost simultaneously, four groups have made remarkably similar and provocative observations [6-9]. Many thousands of sites of mRNA editing have now been revealed in more than 1,600 human genes. But a remarkable additional finding has