Modifications of RNA affect its function and stability. RNA editing is unique among these modifications because it not only alters the cellular fate of RNA molecules but also alters their sequence relative to the genome. The most common type of RNA editing is A-to-I editing by double-stranded RNA-specific adenosine deaminase (ADAR) enzymes. Recent transcriptomic studies have identified a number of 'recoding' sites at which A-to-I editing results in non-synonymous substitutions in protein-coding sequences. Many of these recoding sites are conserved within (but not usually across) lineages, are under positive selection and have functional and evolutionary importance. However, systematic mapping of the editome across the animal kingdom has revealed that most A-to-I editing sites are located within mobile elements in non-coding parts of the genome. Editing of these non-coding sites is thought to have a critical role in protecting against activation of innate immunity by self-transcripts. Both recoding and non-coding events have implications for genome evolution and, when deregulated, may lead to disease. Finally, ADARs are now being adapted for RNA engineering purposes.
Bibliographical noteFunding Information:
The authors thank O. Gabay for the graphical work and B. Knisbacher and the Levanon laboratory members for fruitful discussions. The authors also thank J. Rosenthal and J-B. Li for critical reading of the manuscript. This work was supported by the European Research Council (grant 311257), the Israel Science Foundation (1380/14) and the Minerva Stiftung ARCHES award from the Federal German Ministry for Education and Research (BMBF) to E.Y.L. E.E. was supported by the Israel Science Foundation (2673/17) and the United States-Israel Binational Science Foundation (094/2013).
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