Journal article
Adenosine-to-inosine RNA editing by ADAR1 is essential for normal murine erythropoiesis
BJ Liddicoat, JC Hartner, R Piskol, G Ramaswami, AM Chalk, PD Kingsley, VG Sankaran, M Wall, LE Purton, PH Seeburg, J Palis, SH Orkin, J Lu, JB Li, CR Walkley
Experimental Hematology | ELSEVIER SCIENCE INC | Published : 2016
Abstract
Adenosine deaminases that act on RNA (ADARs) convert adenosine residues to inosine in double-stranded RNA. In vivo, ADAR1 is essential for the maintenance of hematopoietic stem/progenitors. Whether other hematopoietic cell types also require ADAR1 has not been assessed. Using erythroid- and myeloid-restricted deletion of Adar1, we demonstrate that ADAR1 is dispensable for myelopoiesis but is essential for normal erythropoiesis. Adar1-deficient erythroid cells display a profound activation of innate immune signaling and high levels of cell death. No changes in microRNA levels were found in ADAR1-deficient erythroid cells. Using an editing-deficient allele, we demonstrate that RNA editing is t..
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Awarded by Deutscher Akademischer Austauschdienst
Funding Acknowledgements
The authors thank M. Smyth for Ifnar<SUP>-/-</SUP> and Ifngr<SUP>-/-</SUP>; the SVH BioResources Centre; and the SVI Flow Cytometry Core Facility (M. Thomson). This work was supported by grants from the Leukaemia Foundation (C.R.W.); the Leukaemia Foundation (doctoral scholarship to B.J.L.); the National Health and Medical Research Council (NHMRC Project Grant APP1021216, NHMRC Career Development Award APP559016 to C.R.W.; NHMRC Research Fellowship Grant #1003339 to L.E.P.); the German Academic Exchange Service (postdoctoral fellowship); a Stanford Dean's Fellowship to R.P.; Stanford Genome National Institutes of Health Grant R01GM102484, the Ellison Medical Foundation; Stanford University Department of Genetics (J.B.L.); National Institutes of Health (Grant R01HL116364 to J.P.); and the Victorian State Government OIS Program (to St. Vincent's Institute). S.H.O. is an investigator at the Howard Hughes Medical Institute. C.R.W. was the Leukaemia Foundation Phillip Desbrow Senior Research Fellow.