ADAR Regulates RNA Editing, Transcript Stability, and Gene Expression

•We identify 50,000 editing sites in various human RNA species•ADAR1 is the key editing protein, whereas ADAR2 has more influence on gene expression•ADAR proteins regulate gene expression independently of editing•ADAR1 and HuR cooperate by binding to common RNA targets to regulate their stability

SummaryAdenosine deaminases acting on RNA (ADARs) convert adenosine to inosine, which is then recognized as guanosine. To study the role of ADAR proteins in RNA editing and gene regulation, we sequenced and compared the DNA and RNA of human B cells. Then, we followed up the findings experimentally with siRNA knockdown and RNA and protein immunoprecipitations. The results uncovered over 60,000 A-to-G editing sites and several thousand genes whose expression levels are influenced by ADARs. Of these ADAR targets, 90% were identified. Our results also reveal that ADAR regulates transcript stability and gene expression through interaction with HuR (ELAVL1). These findings extend the role of ADAR and show that it cooperates with other RNA-processing proteins to regulate the sequence and expression of transcripts in human cells.

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