An in-depth profiling of the human RNA editome. Homo sapiens

RNA editing represents a critical post-transcriptional event that recodes hereditary information and modulates mammalian development. Dysregulation of the editing process alters transcriptome and proteome signatures and may contribute to human pathogenesis. Thorough characterization of this process, which is manifested in single nucleotide changes in the RNA transcripts, depends critically on a high-throughput and false-positives-aware approach. Through the combination of transcriptome resequencing at significant depth and stringent bioinformatics analysis, we report here an exact and comprehensive profiling of RNA editome by comparing the genome and transcriptome sequences from the same individual. We identified 32,550 RNA editing events in the expressed sequences of protein-coding and noncoding genes. A-to-I(G) changes predominated in this portfolio and attributes previously ascribed to ADAR-mediated editing was observed, thus validating our approach. Interestingly, comparison of our dataset with known sites revealed that only less than 10% of RNA editing sites was annotated previously, asserting a significant contribution of editing at the nucleotide level to transcript and individual variation. Furthermore, we identified thousands of non-A-to-G nucleotide changes in the transcriptome, which occurred at significantly higher-than-noise rate and were supported by Sanger sequencing. Cross-talk between RNA editing and other post-transcriptional regulatory processes was also evident in our study, further implicating RNA editing in enriching the transcriptome. Together, our large-scale study on one individual significantly expanded the repertoire of human RNA editome and substantiated its epigenetic role in shaping transcriptome landscape and inter-individual diversity.