Genomic Positional Dissection of RNA Editomes in Tumor and Normal Samples

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.

Comprehensive Characterization of RNA Editing in Primary Gastric Adenocarcinoma through RNA-seq Data Analysis

“…Also, frequency of editing sites were correlated with size of chromosomes. These results are in a good agreement with Chigaev et al study, who reported that correlation of editing frequency with protein coding genes is stronger than lincRNA density [80]. However, these correlation could result from the bias of the library preparation step of RNA sequencing projects.…”

“…Our analyses found signi cant number of editing sites, vast majority of them harbored in 3´UTR regions, which has been reported in previous studies [80,82]. Also a few novel editing sites were found, which were reported for the rst time in the current study.…”

RNA Editing Signatures Predict Response to Immunotherapies in Melanoma Patients

“…The resulting I-U base-pair is significantly less stable than the replaced A-U base-pair causing destabilization of dsRNA 10 . These modifications have vital roles in cellular homeostasis, as unedited dsRNA regions are recognized by human cells as viral contaminants and trigger strong immune responses 7,10 . Importantly for our study, the resulting I base is recognized as a Guanine (G) during library construction, enabling the identification of A-I editing sites from RNA-Seq data using a number of available computational tools [11][12][13] .…”

“…enzymatically inactive)) catalyzes the deamination of Adenines (A) within doublestranded regions of RNA (dsRNA) into Inosines (I), in a process known as A-to-I editing 10 . The resulting I-U base-pair is significantly less stable than the replaced A-U base-pair causing destabilization of dsRNA 10 .…”

“…enzymatically inactive)) catalyzes the deamination of Adenines (A) within doublestranded regions of RNA (dsRNA) into Inosines (I), in a process known as A-to-I editing 10 . The resulting I-U base-pair is significantly less stable than the replaced A-U base-pair causing destabilization of dsRNA 10 . These modifications have vital roles in cellular homeostasis, as unedited dsRNA regions are recognized by human cells as viral contaminants and trigger strong immune responses 7,10 .…”