@article{b7afada57b094b82a68df2703dcddf61,
title = "Isoforms of RNA-Editing Enzyme ADAR1 Independently Control Nucleic Acid Sensor MDA5-Driven Autoimmunity and Multi-organ Development",
abstract = "Mutations in ADAR, which encodes the ADAR1 RNA-editing enzyme, cause Aicardi-Gouti{\`e}res syndrome (AGS), a severe autoimmune disease associated with an aberrant type I interferon response. How ADAR1 prevents autoimmunity remains incompletely defined. Here, we demonstrate that ADAR1 is a specific and essential negative regulator of the MDA5-MAVS RNA sensing pathway. Moreover, we uncovered a MDA5-MAVS-independent function for ADAR1 in the development of multiple organs. We showed that the p150 isoform of ADAR1 uniquely regulated the MDA5 pathway, whereas both the p150 and p110 isoforms contributed to development. Abrupt deletion of ADAR1 in adult mice revealed that both of these functions were required throughout life. Our findings delineate genetically separable roles for both ADAR1 isoforms in vivo, with implications for the human diseases caused by ADAR mutations.",
author = "Kathleen Pestal and Funk, {Cory C.} and Snyder, {Jessica M.} and Price, {Nathan D.} and Treuting, {Piper M.} and Stetson, {Daniel B.}",
note = "Funding Information: We are grateful to Stuart Orkin for providing mice with the Adar conditional allele; to Ming R. Loo and Michael Gale, Jr., for providing Mavs −/− , Ifih1 −/− , and Ddx58 −/− mice; to Shizuo Akira for the Ddx58 −/− mice; to Marco Colonna for the Ifih1 −/− mice; to Glen Barber for Tmem173 −/− mice; to M.B.A. Oldstone for Adar p150 +/− gametes; to Yanick Crow for helpful insights; to Stephanie Cambier for bioinformatics analysis; to Brian Johnson, Kerrie Allen, and the staff of UW Histology and Imaging Core for their technical expertise; and to members of the D.B.S. and M. Bevan labs for helpful discussions. D.B.S. is a scholar of the Rita Allen Foundation and a Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Disease. This work was supported by grants from the NIH (AI084914 to D.B.S. and N.D.P.; T32GM007270 to K.P.) and the Lupus Research Institute (D.B.S.). Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",
year = "2015",
month = nov,
day = "17",
doi = "10.1016/j.immuni.2015.11.001",
language = "English (US)",
volume = "43",
pages = "933--944",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "5",
}