Comprehensive analysis of RNA-Seq data reveals extensive RNA editing in a human transcriptome

Zhiyu Peng, Yanbing Cheng, Bertrand Chin-Ming Tan, Lin Kang, Zhijian Tian, Yuankun Zhu, Wenwei Zhang, Yu Liang, Xueda Hu, Xuemei Tan, Jing Guo, Zirui Dong, Yan Liang, Li Bao, Jun Wang

RNA editing is a post-transcriptional event that recodes hereditary information. Here we describe a comprehensive profile of the RNA editome of a male Han Chinese individual based on analysis of ∼767 million sequencing reads from poly(A)(+), poly(A)(-) and small RNA samples. We developed a computational pipeline that carefully controls for false positives while calling RNA editing events from genome and whole-transcriptome data of the same individual. We identified 22,688 RNA editing events in noncoding genes and introns, untranslated regions and coding sequences of protein-coding genes. Most changes (∼93%) converted A to I(G), consistent with known editing mechanisms based on adenosine deaminase acting on RNA (ADAR). We also found evidence of other types of nucleotide changes; however, these were validated at lower rates. We found 44 editing sites in microRNAs (miRNAs), suggesting a potential link between RNA editing and miRNA-mediated regulation. Our approach facilitates large-scale studies to profile and compare editomes across a wide range of samples.