Adenosine deaminase acting on RNA-1 is essential for early B lymphopoiesis

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Adenosine deaminase acting on RNA-1 is essential for early B lymphopoiesis
Title:
Adenosine deaminase acting on RNA-1 is essential for early B lymphopoiesis
Journal Title:
Cell Reports
Publication Date:
22 November 2022
Citation:
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.
Description:
ISSN:
2211-1247