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

Jae Hoon Bahn, Jaegyoon Ahn, Xianzhi Lin, Qing Zhang, Jae Hyung Lee, Mete Civelek, Xinshu Xiao

Research output: Contribution to journalArticlepeer-review

87 Citations (Scopus)

Abstract

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 3â €2 UTR usage and miRNA biogenesis. We observe that binding of ADAR1 to 3â €2 UTRs precludes binding by other factors, causing 3â €2 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.

Original languageEnglish
Article number6355
JournalNature Communications
Volume6
DOIs
Publication statusPublished - 9 Mar 2015

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