Chen, W., Li, Y., Ruan, G.-X., Huang, H., Zhang, R., Wang, J., Ouyang, Y., Li, Y., Xu, S., & Ou, X. (2022). Adenosine deaminase acting on RNA-1 is essential for early B lymphopoiesis. Cell Reports, 41(8), 111687. https://doi.org/10.1016/j.celrep.2022.111687
Abstract:
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.
License type:
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Funding Info:
This research is supported by core funding from: the Agency for Science, Technology, and Research, Singapore
Grant Reference no. : NA
This study was supported by Guangdong Basic and Applied Basic Research Foundation (grant 2020A1515010262), National Natural Science Foundation of China (grant 32170882), Shenzhen Science and Technology Innovation Commission (grant JCYJ20190809161807432.