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.

• MeSH
• adenosindeaminasa chemie   genetika   MeSH
• adenosinmonofosfát metabolismus   MeSH
• bodová mutace genetika   MeSH
• degenerace nervu patologie   MeSH
• Drosophila melanogaster genetika   imunologie   MeSH
• editace RNA genetika   MeSH
• katalýza MeSH
• lokomoce MeSH
• messenger RNA genetika   metabolismus   MeSH
• mozek metabolismus   MeSH
• přirozená imunita genetika   MeSH
• proteinové domény MeSH
• proteiny Drosophily chemie   genetika   metabolismus   MeSH
• regulace genové exprese MeSH
• ribonukleasa III metabolismus   MeSH
• RNA-helikasy metabolismus   MeSH
• stárnutí patologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH