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  RNA editing by ADAR1 prevents MDA5 sensing of endogenous dsRNA as nonself

Liddicoat, B. J., Piskol, R., Chalk, A. M., Ramaswami, G., Higuchi, M., Hartner, J. C., et al. (2015). RNA editing by ADAR1 prevents MDA5 sensing of endogenous dsRNA as nonself. Science, 349(6252), 1115-1120. doi:10.1126/science.aac7049.

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Liddicoat, Brian J., Author
Piskol, Robert, Author
Chalk, Alistair M., Author
Ramaswami, Gokul, Author
Higuchi, Miyoko1, Author              
Hartner, Jochen C.1, Author              
Li, Jin Billy, Author
Seeburg, Peter H.1, Author              
Walkley, Carl R., Author
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1Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497704              

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 Abstract: Adenosine-to-inosine (A-to-I) editing is a highly prevalent posttranscriptional modification of RNA, mediated by ADAR (adenosine deaminase acting on RNA) enzymes. In addition to RNA editing, additional functions have been proposed for ADAR1. To determine the specific role of RNA editing by ADAR1, we generated mice with an editing-deficient knock-in mutation (Adar1(E861A), where E861A denotes Glu(861)→Ala(861)). Adar1(E861A/E861A) embryos died at ~E13.5 (embryonic day 13.5), with activated interferon and double-stranded RNA (dsRNA)-sensing pathways. Genome-wide analysis of the in vivo substrates of ADAR1 identified clustered hyperediting within long dsRNA stem loops within 3' untranslated regions of endogenous transcripts. Finally, embryonic death and phenotypes of Adar1(E861A/E861A) were rescued by concurrent deletion of the cytosolic sensor of dsRNA, MDA5. A-to-I editing of endogenous dsRNA is the essential function of ADAR1, preventing the activation of the cytosolic dsRNA response by endogenous transcripts.

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Language(s): eng - English
 Dates: 2015-06-012015-07-132015-09-04
 Publication Status: Published in print
 Pages: 7
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 Rev. Type: Peer
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Title: Science
Source Genre: Journal
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Publ. Info: Washington, D.C. : American Association for the Advancement of Science
Pages: - Volume / Issue: 349 (6252) Sequence Number: - Start / End Page: 1115 - 1120 Identifier: ISSN: 0036-8075
CoNE: https://pure.mpg.de/cone/journals/resource/991042748276600_1