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Schlagwörter:
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Zusammenfassung:
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.
