The spliceosome component Usp39 controls B cell development by regulating immunoglobulin gene rearrangement
Gui-Xin Ruan,
Yuxing Li,
Wenjing Chen,
Hengjun Huang,
Rui Zhang,
Changxu Chen,
Kong-Peng Lam,
Shengli Xu,
Xijun Ou
Affiliations
Gui-Xin Ruan
Harbin Institute of Technology, Harbin 150001, China; Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China
Yuxing Li
Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China
Wenjing Chen
Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China
Hengjun Huang
Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China
Rui Zhang
Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China
Changxu Chen
Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China
Kong-Peng Lam
Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore; Departments of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore; Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore
Shengli Xu
Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore
Xijun Ou
Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China; Corresponding author
Summary: 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.
