Adenosine-to-inosine RNA editing by ADAR1 is essential for normal murine 
erythropoiesis

Liddicoat, Brian J.; Hartner, Jochen C.; Piskol, Robert; Ramaswami, Gokul; Chalka, Alistair M.; Kingsley, Paul D.; Sankaran, Vijay G.; Wall, Meaghan; Purton, Louise E.; Seeburg, Peter H.; Palis, James; Orkin, Stuart H.; Lu, Jun; Li, Jin Billy; Walkley, Carl R.

doi:10.1016/j.exphem.2016.06.250

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Adenosine-to-inosine RNA editing by ADAR1 is essential for normal murine erythropoiesis

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Seeburg, Peter H.
Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society;

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http://www.sciencedirect.com/science/article/pii/S0301472X16304374/pdfft?md5=84d3f6837d55ead14ebcde7fa27b39eb&pid=1-s2.0-S0301472X16304374-main.pdf
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http://dx.doi.org/10.1016/j.exphem.2016.06.250
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Citation

Liddicoat, B. J., Hartner, J. C., Piskol, R., Ramaswami, G., Chalka, A. M., Kingsley, P. D., et al. (2016). Adenosine-to-inosine RNA editing by ADAR1 is essential for normal murine erythropoiesis. Experimental Hematology, 44(10), 947-963. doi:10.1016/j.exphem.2016.06.250.

Cite as: http://hdl.handle.net/11858/00-001M-0000-002C-B282-6

Abstract

Adenosine deaminases that act on RNA (ADARs) convert adenosine residues to inosine in doublestranded 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 microRNAlevels were found inADAR1-deficient erythroid cells. Using an editing-deficient allele, we demonstrate thatRNA editing is the essential function ofADAR1 during erythropoiesis.Mapping of adenosine-to-inosine editing in purified erythroid cells identified clusters of hyperedited adenosines located in long 3’-untranslated regions of erythroid-specific transcripts and these are ADAR1-specific editing events. ADAR1-mediated RNA editing is essential for normal erythropoiesis.