Editing the flow of information

The central dogma of molecular biology states that genetic information stored in DNA is transcribed and subsequently translated into proteins. The information should thereby be copied from DNA into RNA without changes to the information. 1 The relatively constant number of genes among eukaryotes of different complexity has, however, challenged this concept of a rigid flow of information. For quite some time now alternative splicing and post-translational protein modifications have been recognized as means to diversify genetic information and protein function, thereby contributing to cellular and organismic complexity. The recognition of RNA editing as a major player in the alteration of genetic information has only occurred in recent years. First discovered more than 25 y ago, RNA-editing has long been believed to be an oddity of nature restricted to biological niches such as trypanosome mitochondria or plant organelles. Even when RNA-editing was discovered in metazoan nuclear RNA in the late '80s and early '90s it was still believed to be a rare event. Only with the onset of powerful bioinformatics combined with next generation RNA sequencing the full extent of RNA editing was recognized. 4-6 Today, in the human transcriptome hundreds of thousands of editing combination are predicted, leading to a transcriptome variability that may reach similar levels or even outnumber that generated by alternative splicing. The large number of detected editing events makes a prediction of their functional consequences virtually impossible. As different as the organisms in which RNA editing has been detected are the underlying machineries. Two basic types of RNA-editing can be distinguished. On the one hand, nucleotide conversion is achieved by deaminating cytosines or adenosines to generate uridines or inosines, respectively. On the other hand, nucleotide insertion and deletion events are the predominant type of RNA-editing found in organellar RNA. Also, depending on the organism, the machineries involved in RNA-editing are sometimes known in much detail, while in other cases only candidate genes have been identified. Besides the study of the machineries involved, their spatio-termporal regulation, their specific targeting, and the consequences of editing pose obvious open questions. The current book on RNA editing covers several aspects of RNA editing in 10 chapters. Overall, the book has a clear emphasis on adenosine-deamination type editing mediated by ADARs. Five chapters deal with this type of RNA editing in one way or another. Here, the impact of adenosine deamination on both coding and non-coding transcripts, the interaction with …