A-to-I nonsynonymous RNA editing was significantly enriched in the ubiquitination site and correlated with clinical features and immune response

Abstract

RNA editing is a post-transcriptional process that alters RNA sequence in a site-specific manner. A-to-I editing is the most abundant as well as the most well-studied type of RNA editing. About 0.5% of A-to-I editing sites were located in the coding regions. Despite of thousands of identified A-to-I nonsynonymous editing sites, the function of nonsynonymous editing was poorly studied. Here, we found that the nonsynonymous editing was significantly enriched in the ubiquitination site, compared to the synonymous editing. This enrichment was also in a modification type dependent manner, since it was not significantly enriched in other modification types. This observation was consistent with previous study that the codons for lysine (AAG and AAA) were enriched in the preferred deamination site for RNA editing. The peptides from proteomic data in CPTAC supported that mRNAs harboring edited ubiquitination sites can be translated into protein in cells. We identified the editing sites on ubiquitination site were significantly differential edited between tumor and para-tumor samples as well as among different subtypes in TCGA datasets and also correlated with clinical outcome, especially for the nonsynonymous editing sites on GSTM5, WDR1, SSR4 and PSMC4. Finally, the enrichment analysis revealed that the function of these above genes was specifically enriched in the immune response pathway. Our study shed a light on understanding the functions of nonsynonymous editing in tumorigenesis and provided nonsynonymous editing targets for potential cancer diagnosis and therapy.