Genomic analysis of ADAR1 binding and its involvement in multiple RNA processing pathways

• DOI: 10.1038/ncomms7355
• Publication Date: 2015-03-09T12:35:13Z
• Authors: Jae Hoon Bahn; Jaegyoon Ahn; Xianzhi Lin; Qing Zhang; Jae-Hyung Lee; Mete Civelek; Xinshu Xiao
• Keywords: Ribonuclease III; 570; Adenosine Deaminase; 1.1 Normal biological development and functioning; Molecular Sequence Data; Bioinformatics and Computational Biology; 610; Cell Fractionation; Article; Cell Line; 03 medical and health sciences; Genetics; Humans; Immunoprecipitation; DNA Primers; 0303 health sciences; Base Sequence; Sequence Analysis, RNA; Human Genome; RNA-Binding Proteins; Biological Sciences; MicroRNAs; RNA; Generic health relevance; Sequence Analysis; Biotechnology; Protein Binding

Adenosine deaminases acting on RNA (ADARs) are the primary factors underlying adenosine to inosine (A-to-I) editing in metazoans. Here we report the first global study of ADAR1-RNA interaction in human cells using CLIP-seq. A large number of CLIP sites are observed in Alu repeats, consistent with ADAR1's function in RNA editing. Surprisingly, thousands of other CLIP sites are located in non-Alu regions, revealing functional and biophysical targets of ADAR1 in the regulation of alternative 3' UTR usage and miRNA biogenesis. We observe that binding of ADAR1 to 3' UTRs precludes binding by other factors, causing 3' UTR lengthening. Similarly, ADAR1 interacts with DROSHA and DGCR8 in the nucleus and possibly out-competes DGCR8 in primary miRNA binding, which enhances mature miRNA expression. These functions are dependent on ADAR1's editing activity, at least for a subset of targets. Our study unfolds a broad landscape of the functional roles of ADAR1.