RNA editing by ADAR1 prevents MDA5 sensing of endogenous dsRNA as nonself
The University of Melbourne · St Vincent's Hospital Melbourne · +4 more institutions
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…
Citation impact
- FWCI
- 27.40
- Percentile
- 100%
- References
- 41
Authors
9- BLBrian Liddicoat
The University of Melbourne, St Vincent's Hospital Melbourne, St Vincents Institute of Medical Research
- RPRobert Piskol
Stanford University
- AMAlistair M. Chalk
The University of Melbourne, St Vincent's Hospital Melbourne, St Vincents Institute of Medical Research
- GRGokul Ramaswami
Stanford University
- MHMiyoko Higuchi
Max Planck Institute for Medical Research
Topics & keywords
- RNA editing
- ADAR
- RNA silencing
- MDA5
- Biology
- RNA
- Molecular biology
- Adenosine deaminase