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

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Listed:
  • Jae Hoon Bahn

    (University of California Los Angeles)

  • Jaegyoon Ahn

    (University of California Los Angeles)

  • Xianzhi Lin

    (University of California Los Angeles)

  • Qing Zhang

    (University of California Los Angeles)

  • Jae-Hyung Lee

    (University of California Los Angeles
    Present address: Department of Life and Nanopharmaceutical Sciences, Department of Maxillofacial Biomedical Engineering, School of Dentistry, Kyung Hee University, Seoul, Korea)

  • Mete Civelek

    (University of California Los Angeles)

  • Xinshu Xiao

    (University of California Los Angeles)

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 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.

Suggested Citation

  • Jae Hoon Bahn & Jaegyoon Ahn & Xianzhi Lin & Qing Zhang & Jae-Hyung Lee & Mete Civelek & Xinshu Xiao, 2015. "Genomic analysis of ADAR1 binding and its involvement in multiple RNA processing pathways," Nature Communications, Nature, vol. 6(1), pages 1-13, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7355
    DOI: 10.1038/ncomms7355
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    Cited by:

    1. Suba Rajendren & Xiang Ye & William Dunker & Antiana Richardson & John Karijolich, 2023. "The cellular and KSHV A-to-I RNA editome in primary effusion lymphoma and its role in the viral lifecycle," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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