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Adar RNA editing-dependent and -independent effects are required for brain and innate immune functions in Drosophila

Author

Listed:
  • Patricia Deng

    (Stanford University)

  • Anzer Khan

    (Central European Institute of Technology, Masaryk University
    National Centre for Biomolecular Research, Faculty of Science, Masaryk University)

  • Dionna Jacobson

    (Stanford University)

  • Nagraj Sambrani

    (Central European Institute of Technology, Masaryk University)

  • Leeanne McGurk

    (MRC Institute of Genetics and Molecular Medicine, Western General Hospital)

  • Xianghua Li

    (MRC Institute of Genetics and Molecular Medicine, Western General Hospital)

  • Aswathy Jayasree

    (Central European Institute of Technology, Masaryk University)

  • Jan Hejatko

    (Central European Institute of Technology, Masaryk University
    National Centre for Biomolecular Research, Faculty of Science, Masaryk University)

  • Galit Shohat-Ophir

    (The Faculty of Life Sciences and The Multidisciplinary Brain Research Center, Bar Ilan University)

  • Mary A. O’Connell

    (Central European Institute of Technology, Masaryk University)

  • Jin Billy Li

    (Stanford University)

  • Liam P. Keegan

    (Central European Institute of Technology, Masaryk University)

Abstract

ADAR RNA editing enzymes are high-affinity dsRNA-binding proteins that deaminate adenosines to inosines in pre-mRNA hairpins and also exert editing-independent effects. We generated a Drosophila AdarE374A mutant strain encoding a catalytically inactive Adar with CRISPR/Cas9. We demonstrate that Adar adenosine deamination activity is necessary for normal locomotion and prevents age-dependent neurodegeneration. The catalytically inactive protein, when expressed at a higher than physiological level, can rescue neurodegeneration in Adar mutants, suggesting also editing-independent effects. Furthermore, loss of Adar RNA editing activity leads to innate immune induction, indicating that Drosophila Adar, despite being the homolog of mammalian ADAR2, also has functions similar to mammalian ADAR1. The innate immune induction in fly Adar mutants is suppressed by silencing of Dicer-2, which has a RNA helicase domain similar to MDA5 that senses unedited dsRNAs in mammalian Adar1 mutants. Our work demonstrates that the single Adar enzyme in Drosophila unexpectedly has dual functions.

Suggested Citation

  • Patricia Deng & Anzer Khan & Dionna Jacobson & Nagraj Sambrani & Leeanne McGurk & Xianghua Li & Aswathy Jayasree & Jan Hejatko & Galit Shohat-Ophir & Mary A. O’Connell & Jin Billy Li & Liam P. Keegan, 2020. "Adar RNA editing-dependent and -independent effects are required for brain and innate immune functions in Drosophila," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15435-1
    DOI: 10.1038/s41467-020-15435-1
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    Cited by:

    1. Katarzyna Niescierowicz & Leszek Pryszcz & Cristina Navarrete & Eugeniusz Tralle & Agata Sulej & Karim Abu Nahia & Marta Elżbieta Kasprzyk & Katarzyna Misztal & Abhishek Pateria & Adrianna Pakuła & Ma, 2022. "Adar-mediated A-to-I editing is required for embryonic patterning and innate immune response regulation in zebrafish," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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