Computational detection and functional analysis of human tissue-specific A-to-I RNA editing

A-to-I RNA editing is a widespread post-transcriptional modification event in vertebrates. It could increase transcriptome and proteome diversity through recoding the genomic information and cross-linking other regulatory events, such as those mediated by alternative splicing, RNAi and microRNA (miRNA). Previous studies indicated that RNA editing can occur in a tissue-specific manner in response to the requirements of the local environment. We set out to systematically detect tissue-specific A-to-I RNA editing sites in 43 human tissues using bioinformatics approaches based on the Fisher's exact test and the Benjamini & Hochberg false discovery rate (FDR) multiple testing correction. Twenty-three sites in total were identified to be tissue-specific. One of them resulted in an altered amino acid residue which may prevent the phosphorylation of PARP-10 and affect its activity. Eight and two tissue-specific A-to-I RNA editing sites were predicted to destroy putative exonic splicing enhancers (ESEs) and exonic splicing silencers (ESSs), respectively. Brain-specific and ovary-specific A-to-I RNA editing sites were further verified by comparing the cDNA sequences with their corresponding genomic templates in multiple cell lines from brain, colon, breast, bone marrow, lymph, liver, ovary and kidney tissue. Our findings help to elucidate the role of A-to-I RNA editing in the regulation of tissue-specific development and function, and the approach utilized here can be broadened to study other types of tissue-specific substitution editing.