| First Author | Chen W | Year | 2022 |
| Journal | Cell Rep | Volume | 41 |
| Issue | 8 | Pages | 111687 |
| PubMed ID | 36417848 | Mgi Jnum | J:332179 |
| Mgi Id | MGI:7407983 | Doi | 10.1016/j.celrep.2022.111687 |
| Citation | Chen W, et al. (2022) Adenosine deaminase acting on RNA-1 is essential for early B lymphopoiesis. Cell Rep 41(8):111687 |
| abstractText | Adenosine deaminase acting on RNA-1 (ADAR1) is a ubiquitously expressed RNA deaminase catalyzing adenosine-to-inosine editing to prevent hyperactivated cytosolic double-stranded RNA (dsRNA) response mediated by MDA5. Here, we demonstrate that ADAR1 is essential for early B lymphopoiesis from late pro-B and large pre-B cell stages onward. ADAR1 exerts its requisite role via both MDA5-dependent and -independent pathways. Interestingly, the MDA5-dependent mechanisms regulate early pro-B to large pre-B cell transition by promoting early B cell survival. In contrast, the MDA5-independent mechanisms control large pre-B to small pre-B cell transition by regulating pre-B cell receptor (pre-BCR) expression. Moreover, we show that protein kinase R (PKR) and oligoadenylate synthetase/ribonuclease (OAS/RNase) L pathways are dispensable for ADAR1's role in early B lymphopoiesis. Importantly, we demonstrate that p150 isoform of ADAR1 exclusively accounts for ADAR1's function in early B lymphopoiesis, and its conventional dsRNA-binding, but not the Z-DNA/RNA-binding or the RNA-editing, activity is required for ADAR1's function in B cell development. Thus, our findings suggest that ADAR1 regulates early B lymphopoiesis through various mechanisms. |
