Abstract
RNA editing is phenomenon that occurs in both protein coding and non-coding RNAs. Increasing evidence have shown that adenosine-to-inosine RNA editing can potentially rendering substantial functional effects throughout the genome. Using RNA editing datasets from two large consortiums: The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) project, we quantitatively analyzed human genome-wide RNA editing events derived from tumor or normal tissues. Generally, a common RNA editing site tends to have a higher editing level in tumors as compared to normal samples. Of the 14 tumor-normal-paired cancer types examined, Eleven of the 14 cancers tested had overall increased RNA editing levels in the tumors. The editomes in cancer or normal tissues were dissected by genomic locations, and significant RNA editing locational difference was found between cancerous and healthy subjects. Additionally, our results indicated a significant correlation between the RNA editing rate and the gene density across chromosomes, highlighted hyper RNA editing clusters through visualization of running RNA editing rates along chromosomes, and identified hyper RNA edited genes (protein-coding genes, lincRNAs, and pseudogenes) that embody a large portion of cancer prognostic predictors. This study reinforces the potential functional effects of RNA editing in protein-coding genes, and also makes a strong foundation for further exploration of RNA editing’s roles in non-coding regions.
Highlights
RNA editing is the molecular process by which ribonucleic acid (RNA) molecule’s nucleotide sequences are modified enzymatically after RNA has been generated by RNA polymerase
These results suggest that one third of the RNA editing sites detected in The Cancer Genome Atlas (TCGA) are cancer specific
TCGA’s cancers were tissue specific, and tissue specific RNA editing sites has been found in normal subjects in GenotypeTissue Expression (GTEx) (Picardi et al, 2017)
Summary
RNA editing is the molecular process by which ribonucleic acid (RNA) molecule’s nucleotide sequences are modified enzymatically after RNA has been generated by RNA polymerase. There are two types of canonical RNA editing: adenine-to-inosine (A-to-I) and cytosine-touracil (C-to-U). The mechanisms of these two types of RNA editing have been thoroughly studied. A-to-I RNA editing accounts for >95% of all reported RNA editing events and over four hundred million adenosine sites in the human genome are presumed to be subject to A-to-I editing (Bazak et al, 2014; Picardi et al, 2017). The mapping of whole-genome RNA editing events leads to the RNA Editing in Coding and Non-coding Regions elucidation of inosinomes (Picardi et al, 2015) or editomes (Diroma et al, 2017)
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