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

DENG, Patricia, Anzer KHAN, Dionna JACOBSON, Nagraj SAMBRANI, Leeanne MCGURK, Xianghua LI, Aswathy JAYASREE, Jan HEJÁTKO, Galit SHOHAT-OPHIR, Mary Anne O'CONNELL, Jin Billy LI and Liam KEEGAN. Adar RNA editing-dependent and -independent effects are required for brain and innate immune functions in Drosophila. Nature Communications. London: Nature Publishing Group, 2020, vol. 11, No 1, p. 1-13. ISSN 2041-1723. Available from: https://dx.doi.org/10.1038/s41467-020-15435-1.

Basic information

• Original name: Adar RNA editing-dependent and -independent effects are required for brain and innate immune functions in Drosophila
• Authors: DENG, Patricia, Anzer KHAN (356 India, belonging to the institution), Dionna JACOBSON, Nagraj SAMBRANI (356 India, belonging to the institution), Leeanne MCGURK, Xianghua LI, Aswathy JAYASREE (356 India, belonging to the institution), Jan HEJÁTKO (203 Czech Republic, belonging to the institution), Galit SHOHAT-OPHIR, Mary Anne O'CONNELL (372 Ireland, guarantor, belonging to the institution), Jin Billy LI and Liam KEEGAN (372 Ireland, belonging to the institution).
• Edition: Nature Communications, London, Nature Publishing Group, 2020, 2041-1723.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 10608 Biochemistry and molecular biology
• Country of publisher: United Kingdom of Great Britain and Northern Ireland
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 14.919
• RIV identification code: RIV/00216224:14740/20:00114707
• Organization unit: Central European Institute of Technology
• Doi: http://dx.doi.org/10.1038/s41467-020-15435-1
• UT WoS: 000522436700007
• Keywords in English: Gene expression; Innate immunity; Neuroscience; RNA editing
• Tags: rivok
• Tags: International impact, Reviewed

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 Adar(E374A) 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. Human RNA editing enzymes ADAR1 and ADAR2 are required for innate immune functions and neurological functions, respectively. Here, the authors show that Drosophila Adar has both innate immune and brain functions, despite being the homolog of mammalian ADAR2.

Links

• EF16_013/0001775, research and development project: Name: Modernizace a podpora výzkumných aktivit národní infrastruktury pro biologické a medicínské zobrazování Czech-BioImaging
• GA19-16963S, research and development project: Name: Genetický model myši pro studium kontroly interferonu a zánětu

Investor: Czech Science Foundation

• 621368, interní kód MU: Name: The ERA Chair Culture as a Catalyst to Maximize the Potential of CEITEC (Acronym: CEITEC_ERA)

Investor: European Union, The ERA Chair Culture as a Catalyst to Maximize the Potential of CEITEC, Capacities