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ADAR1 interaction with Z-RNA promotes editing of endogenous double-stranded RNA and prevents MDA5-dependent immune activation

Richard de Reuver (UGent) , Evelien Dierick (UGent) , Bartosz Wiernicki, Katrien Staes (UGent) , Leen Seys (UGent) , Ellen De Meester (UGent) , Tuur Muyldermans (UGent) , Alexander Botzki (UGent) , Bart Lambrecht (UGent) , Filip Van Nieuwerburgh (UGent) , et al.
(2021) CELL REPORTS. 36(6).
Author
Organization
Abstract
Loss of function of adenosine deaminase acting on double-stranded RNA (dsRNA)-1 (ADAR1) causes the severe autoinflammatory disease Aicardi-Goutie' res syndrome (AGS). ADAR1 converts adenosines into inosines within dsRNA. This process called A-to-I editing masks self-dsRNA from detection by the antiviral dsRNA sensor MDA5. ADAR1 binds to dsRNA in both the canonical A-form and the poorly defined Z conformation (Z-RNA). Mutations in the Z-RNA-binding Za domain of ADAR1 are common in patients with AGS. How loss of ADAR1/Z-RNA interaction contributes to disease development is unknown. We demonstrate that abrogated binding of ADAR1 to Z-RNA leads to reduced A-to-I editing of dsRNA structures formed by base pairing of inversely oriented short interspersed nuclear elements. Preventing ADAR1 binding to Z-RNA triggers an MDA5/MAVS-mediated type I interferon response and leads to the development of lethal autoinflammation in mice. This shows that the interaction between ADAR1 and Z-RNA restricts sensing of self-dsRNA and prevents AGS development.
Keywords
I INTERFERON, ADENOSINE-DEAMINASE, ADAPTER PROTEIN, Z-ALPHA, RESPONSES, DOMAIN, IDENTIFICATION, RETROELEMENTS, DEFICIENCY, MUTATIONS

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MLA
de Reuver, Richard, et al. “ADAR1 Interaction with Z-RNA Promotes Editing of Endogenous Double-Stranded RNA and Prevents MDA5-Dependent Immune Activation.” CELL REPORTS, vol. 36, no. 6, 2021, doi:10.1016/j.celrep.2021.109500.
APA
de Reuver, R., Dierick, E., Wiernicki, B., Staes, K., Seys, L., De Meester, E., … Maelfait, J. (2021). ADAR1 interaction with Z-RNA promotes editing of endogenous double-stranded RNA and prevents MDA5-dependent immune activation. CELL REPORTS, 36(6). https://doi.org/10.1016/j.celrep.2021.109500
Chicago author-date
Reuver, Richard de, Evelien Dierick, Bartosz Wiernicki, Katrien Staes, Leen Seys, Ellen De Meester, Tuur Muyldermans, et al. 2021. “ADAR1 Interaction with Z-RNA Promotes Editing of Endogenous Double-Stranded RNA and Prevents MDA5-Dependent Immune Activation.” CELL REPORTS 36 (6). https://doi.org/10.1016/j.celrep.2021.109500.
Chicago author-date (all authors)
de Reuver, Richard, Evelien Dierick, Bartosz Wiernicki, Katrien Staes, Leen Seys, Ellen De Meester, Tuur Muyldermans, Alexander Botzki, Bart Lambrecht, Filip Van Nieuwerburgh, Peter Vandenabeele, and Jonathan Maelfait. 2021. “ADAR1 Interaction with Z-RNA Promotes Editing of Endogenous Double-Stranded RNA and Prevents MDA5-Dependent Immune Activation.” CELL REPORTS 36 (6). doi:10.1016/j.celrep.2021.109500.
Vancouver
1.
de Reuver R, Dierick E, Wiernicki B, Staes K, Seys L, De Meester E, et al. ADAR1 interaction with Z-RNA promotes editing of endogenous double-stranded RNA and prevents MDA5-dependent immune activation. CELL REPORTS. 2021;36(6).
IEEE
[1]
R. de Reuver et al., “ADAR1 interaction with Z-RNA promotes editing of endogenous double-stranded RNA and prevents MDA5-dependent immune activation,” CELL REPORTS, vol. 36, no. 6, 2021.
@article{8718186,
  abstract     = {{Loss of function of adenosine deaminase acting on double-stranded RNA (dsRNA)-1 (ADAR1) causes the severe autoinflammatory disease Aicardi-Goutie' res syndrome (AGS). ADAR1 converts adenosines into inosines within dsRNA. This process called A-to-I editing masks self-dsRNA from detection by the antiviral dsRNA sensor MDA5. ADAR1 binds to dsRNA in both the canonical A-form and the poorly defined Z conformation (Z-RNA). Mutations in the Z-RNA-binding Za domain of ADAR1 are common in patients with AGS. How loss of ADAR1/Z-RNA interaction contributes to disease development is unknown. We demonstrate that abrogated binding of ADAR1 to Z-RNA leads to reduced A-to-I editing of dsRNA structures formed by base pairing of inversely oriented short interspersed nuclear elements. Preventing ADAR1 binding to Z-RNA triggers an MDA5/MAVS-mediated type I interferon response and leads to the development of lethal autoinflammation in mice. This shows that the interaction between ADAR1 and Z-RNA restricts sensing of self-dsRNA and prevents AGS development.}},
  articleno    = {{109500}},
  author       = {{de Reuver, Richard and Dierick, Evelien and Wiernicki, Bartosz and Staes, Katrien and Seys, Leen and De Meester, Ellen and Muyldermans, Tuur and Botzki, Alexander and Lambrecht, Bart and Van Nieuwerburgh, Filip and Vandenabeele, Peter and Maelfait, Jonathan}},
  issn         = {{2211-1247}},
  journal      = {{CELL REPORTS}},
  keywords     = {{I INTERFERON,ADENOSINE-DEAMINASE,ADAPTER PROTEIN,Z-ALPHA,RESPONSES,DOMAIN,IDENTIFICATION,RETROELEMENTS,DEFICIENCY,MUTATIONS}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{20}},
  title        = {{ADAR1 interaction with Z-RNA promotes editing of endogenous double-stranded RNA and prevents MDA5-dependent immune activation}},
  url          = {{http://doi.org/10.1016/j.celrep.2021.109500}},
  volume       = {{36}},
  year         = {{2021}},
}
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