Abstract
When an RNA editing event occurs within a coding sequence it can lead to a different encoded amino acid. The biological significance of these events remains an open question: they can modulate protein functionality, increase the complexity of transcriptomes or arise from a loose specificity of the involved enzymes. We analysed the editing events in coding regions that produce or not a change in the encoded amino acid (nonsynonymous and synonymous events, respectively) in D. melanogaster and in H. sapiens and compared them with the appropriate random models. Interestingly, our results show that the phenomenon has rather different characteristics in the two organisms. For example, we confirm the observation that editing events occur more frequently in non-coding than in coding regions, and report that this effect is much more evident in H. sapiens. Additionally, in this latter organism, editing events tend to affect less conserved residues. The less frequently occurring editing events in Drosophila tend to avoid drastic amino acid changes. Interestingly, we find that, in Drosophila, changes from less frequently used codons to more frequently used ones are favoured, while this is not the case in H. sapiens.
Highlights
When an RNA editing event occurs within a coding sequence it can lead to a different encoded amino acid
In order to avoid biases due to particular experimental set-ups or to specific genes or tissues, we selected, for D. melanogaster, data derived from the study of Laurent et al This consists of 3581 editing events identified through single-molecule sequencing (SMS) that have been extensively validated with Sanger sequencing
Previous studies reported that many editing events occur at the level of coding regions (CDS) in D. melanogaster[13,19] while this is not the case in human[23,24,25] where a large fraction of editing events affects the untranslated part of the mature transcripts
Summary
When an RNA editing event occurs within a coding sequence it can lead to a different encoded amino acid. These enzymes catalyse the conversion of adenosines to inosines (A to I editing) in double-stranded RNA (dsRNA) substrates[2] When these modifications occur in protein coding exons they can cause nonsynonymous changes leading to a different encoded residue[3]. The advent of the RNA-Seq technology provided a more detailed description of the eukaryotic transcriptomes and highlighted a frequency of RNA editing higher than previously estimated in various organisms, including fly, human, mouse and squid[12,13,14] All these previously unreported events add further complexity to the eukaryotic genomes, but at the same time, make the biological effects of RNA-editing in coding regions less easy to interpret. The comparison of our results with those obtained by performing the same analysis in H. sapiens suggests that the modality and effects of the ADAR-mediated editing in protein coding genes is rather different in the two organisms
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