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@article{1731136,
author = {Deng, Patricia and Khan, Anzer and Jacobson, Dionna and Sambrani, Nagraj and McGurk, Leeanne and Li, Xianghua and Jayasree, Aswathy and Hejátko, Jan and ShohatandOphir, Galit and O'Connell, Mary Anne and Li, Jin Billy and Keegan, Liam},
article_location = {London},
article_number = {1},
doi = {http://dx.doi.org/10.1038/s41467-020-15435-1},
keywords = {Gene expression; Innate immunity; Neuroscience; RNA editing},
language = {eng},
issn = {2041-1723},
journal = {Nature Communications},
title = {Adar RNA editing-dependent and -independent effects are required for brain and innate immune functions in Drosophila},
url = {https://doi.org/10.1038/s41467-020-15435-1},
volume = {11},
year = {2020}
}
TY - JOUR
ID - 1731136
AU - Deng, Patricia - Khan, Anzer - Jacobson, Dionna - Sambrani, Nagraj - McGurk, Leeanne - Li, Xianghua - Jayasree, Aswathy - Hejátko, Jan - Shohat-Ophir, Galit - O'Connell, Mary Anne - Li, Jin Billy - Keegan, Liam
PY - 2020
TI - Adar RNA editing-dependent and -independent effects are required for brain and innate immune functions in Drosophila
JF - Nature Communications
VL - 11
IS - 1
SP - 1-13
EP - 1-13
PB - Nature Publishing Group
SN - 20411723
KW - Gene expression
KW - Innate immunity
KW - Neuroscience
KW - RNA editing
UR - https://doi.org/10.1038/s41467-020-15435-1
L2 - https://doi.org/10.1038/s41467-020-15435-1
N2 - 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.
ER -
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 a Liam KEEGAN. Adar RNA editing-dependent and -independent effects are required for brain and innate immune functions in Drosophila. \textit{Nature Communications}. London: Nature Publishing Group, 2020, roč.~11, č.~1, s.~1-13. ISSN~2041-1723. Dostupné z: https://dx.doi.org/10.1038/s41467-020-15435-1.
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