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

J 2020

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 et. al.

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

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

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

Abstract

V originále

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

Citovat

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.

@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 and 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, vol.~11, No~1, p.~1-13. ISSN~2041-1723. Available from: https://dx.doi.org/10.1038/s41467-020-15435-1.

Detailed Information on Publication Record