Posttranscriptional Gene Regulation by an Editor: ADAR and its Role in RNA Editing

RNA editing is one of several posttranscriptional events that takes place after a new RNA is synthesized, which can lead to dramatic changes from a gene-encoded origin and affect gene regulation globally. The most widespread type of RNA editing is the conversion of adenosine to inosine (A-to-I) in double-stranded (ds) RNA, which is mediated by the adenosine deaminases acting on RNA (ADAR). The RNA itself plays a role in this regulatory process by forming an assortment of secondary structures such as bulges, stem loops, and hairpins. In some cases, ADAR's action on RNA can change the final protein sequence and function of substrates, giving rise to a greater diversity of proteins than by the DNA-encoded genes. Furthermore, ADAR can reduce the double strandedness of RNA duplexes in the cell, and this can have consequences for gene expression through effects on RNA stability, translational efficiency, and RNA interference (RNAi)-mediated gene silencing pathways. It is apparent that the most extensively edited RNA targets are the noncoding regions of mRNA and in the retrotransposable elements found in these areas. Since dsRNA is a requisite for both ADAR RNA editing and the microRNA pathway, it is now clear that these two different systems are converging for the regulation of gene silencing. Disease associated with ADAR misregulation is beginning to be revealed, and now with new RNA targets identified, it is likely that more will emerge due to the global effects produced by ADAR functions.