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

• Published in: Nature communications 2015-03, Vol.6 (1), p.6355-6355, Article 6355
• Main Authors: Bahn, Jae Hoon, Ahn, Jaegyoon, Lin, Xianzhi, Zhang, Qing, Lee, Jae-Hyung, Civelek, Mete, Xiao, Xinshu
• Format: Article
• Language: English
• Subjects: 38; 631/1647/2217; 631/337/1645/1944; Adenosine Deaminase - genetics; Adenosine Deaminase - metabolism; Base Sequence; Cell Fractionation; Cell Line; DNA Primers - genetics; Humanities and Social Sciences; Humans; Immunoprecipitation; MicroRNAs - metabolism; Molecular Sequence Data; multidisciplinary; Protein Binding - genetics; Ribonuclease III - metabolism; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Science; Science (multidisciplinary); Sequence Analysis, RNA
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms7355

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. ADAR1 is an adenosine deaminase that converts adenosine to inosine (A-to-I) mostly on Alu repeats in human RNA. Here by analysing transcriptome-wide ADAR1–RNA interactions, the authors show that ADAR1 also binds non- Alu sequences to regulate alternative 3′ UTR usage and miRNA biogenesis in the nucleus.