Ruan, G.-X., Li, Y., Chen, W., Huang, H., Zhang, R., Chen, C., Lam, K.-P., Xu, S., & Ou, X. (2022). The spliceosome component Usp39 controls B cell development by regulating immunoglobulin gene rearrangement. Cell Reports, 38(6), 110338. https://doi.org/10.1016/j.celrep.2022.110338
Abstract:
The spliceosome is a large ribonucleoprotein complex responsible for pre-mRNA splicing and genome stability maintenance. Disruption of the spliceosome activity may lead to developmental disorders and tumorigenesis. However, the physiological role that the spliceosome plays in B cell development and function is still poorly defined. Here, we demonstrate that ubiquitin-specific peptidase 39 (Usp39), a spliceosome component of the U4/U6.U5 tri-snRNP complex, is essential for B cell development. Ablation of Usp39 in B cell lineage blocks pre-pro-B to pro-B cell transition in the bone marrow, leading to a profound reduction of mature B cells in the periphery. We show that Usp39 specifically regulates immunoglobulin gene rearrangement in a spliceosome-dependent manner, which involves modulating chromatin interactions at the Igh locus. Moreover, our results indicate that Usp39 deletion reduces the pre-malignant B cells in Eμ-Myc transgenic mice and significantly improves their survival.
License type:
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Funding Info:
This work was supported by National Natural Science Foundation of China (grant no. 32170882), the Guangdong Basic and Applied Basic Research Foundation (grant no. 2020A1515010262), and the Shenzhen Science and Technology Innovation Commission (grant no. JCYJ20190809161807432). The authors acknowledge the assistance of SUSTech Core Research Facilities and Laboratory Animal Research Center. The authors thank Prof. Chunhui Hou and Dr. Zaide Niu for the assistance with Hi-C library preparation.