GSE173597
The spliceosome component Usp39 controls B cell development by regulating immunoglobulin gene rearrangement
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. Overall design: RNA-Seq of pre-pro-B cells in Usp39 fl/fl and Usp39 fl/fl mb1-cre mice; RNA-Seq of small pre-B cells in Usp39 fl/fl and Usp39 fl/fl cd19-cre mice; Hi-C-Seq of pre-pro-B cells in Usp39 fl/fl and Usp39 fl/fl mb1-cre mice