A comprehensive RNA editome reveals that edited Azin1 partners with DDX1 to enable hematopoietic stem cell differentiation
Fengjiao Wang 1, Jiahuan He 2, Siqi Liu 2,
Ai Gao 1, Liu Yang 1, Guohuan Sun 1, Wanqiu Ding 3, Chuan-Yun Li 3, Fanglin Gou
1, Manman He 2, Fang Wang 2, Xiaoshuang Wang 2, Xiangnan Zhao 1, Ping Zhu 1 4,
Sha Hao 1 4, Yanni Ma 2, Hui Cheng 1 4, Jia Yu 1 2, Tao Cheng 1 4
Blood.2021 Nov 18;138(20):1939-1952. doi:
10.1182/blood.2021011314.
PMID: 34388251
Abstract
Adenosine-to-inosine
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. The dynamic landscape
of the RNA editome comprises stage- and group-specific and stable editing
patterns, but undergoes 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 an amino acid
change to induce Azin1 protein (AZI) translocation to the nucleus, enhanced AZI
binding affinity for DEAD box polypeptide 1 to alter the chromatin distribution
of the latter, and altered expression of multiple hematopoietic regulators that
ultimately promote HSPC differentiation. Our findings have delineated an
essential role for Azin1 RNA editing in hematopoietic cells, and our data set
is a valuable resource for studying RNA editing on a more general basis.