Adenosine-to-inosine RNA editing by ADAR1 is essential for normal murine erythropoiesis
Journal article
Liddicoat, Brian J., Hartner, Jochen C., Piskol, Robert, Ramaswami, Gokul, Chalk, 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 and Walkley, Carl R.. (2016). Adenosine-to-inosine RNA editing by ADAR1 is essential for normal murine erythropoiesis. Experimental Hematology. 44(10), pp. 947 - 963. https://doi.org/10.1016/j.exphem.2016.06.250
Authors | Liddicoat, Brian J., Hartner, Jochen C., Piskol, Robert, Ramaswami, Gokul, Chalk, 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 and Walkley, Carl R. |
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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 the essential function of ADAR1 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. |
Year | 2016 |
Journal | Experimental Hematology |
Journal citation | 44 (10), pp. 947 - 963 |
Publisher | Elsevier |
ISSN | 0301-472X |
Digital Object Identifier (DOI) | https://doi.org/10.1016/j.exphem.2016.06.250 |
Scopus EID | 2-s2.0-84989936332 |
Page range | 947 - 963 |
Research Group | Mary MacKillop Institute for Health Research |
Publisher's version | File Access Level Controlled |
Grant ID | NHMRC/1021216 |
NHMRC/559016 | |
Place of publication | United States of America |
https://acuresearchbank.acu.edu.au/item/893w8/adenosine-to-inosine-rna-editing-by-adar1-is-essential-for-normal-murine-erythropoiesis
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