Comprehensive RNA editome reveals that edited Azin1 partners with DDX1 to enable hematopoietic stem cell differentiation.

Adenosine-to-inosine (A-to-I) RNA editing and the catalyzing enzyme adenosine deaminase are both essential for hematopoietic development and differentiation. However, the RNA editome during hematopoiesis and the underlying mechanisms are poorly defined. Here, we sorted 12 murine adult hematopoietic cell populations at different stages and identified 30,796 editing sites through RNA sequencing. While the dynamic landscape of the RNA editome comprised of stage/group-specific and stable editing patterns, but also undergoing significant changes during lineage commitment. Notably, we found that antizyme inhibitor 1 (Azin1) was highly edited in hematopoietic stem and progenitor cells (HSPCs). Azin1 editing results in: (i) an amino acid change to induce Azin1 protein (AZI) translocation to the nucleus, (ii) enhanced AZI binding affinity for DEAD box polypeptide 1 (DDX1) to alter the chromatin distribution of the latter, and (iii) altered expression of multiple hematopoietic regulators which ultimately promotes HSPC differentiation. Our findings have delineated an essential role for Azin1 RNA editing in hematopoietic cells, and our dataset constitutes a valuable resource for further study of RNA editing on a more general basis.