Title: Adenosine-to-inosine RNA editing by ADAR1 is essential for normal murine erythropoiesis
Authors: Seeburg, PH
Hartner, JC
Purton, LE
Liddicoat, BJ
Wall, M
Sankaran, VG
Li, JB
Kingsley, PD
Lu, J
Chalk, AM
Orkin, SH
Ramaswami, G
Palis, J
Piskol, R
Walkley, CR
Issue Year: 2016
Series Exp Hematol:
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.
URI: https://publications.svi.edu.au/publications/2463
Other Identifiers 44 (10): 947-63
Publication type Article