The spliceosome component Usp39 controls B cell development by regulating immunoglobulin gene rearrangement. 2022

Gui-Xin Ruan, and Yuxing Li, and Wenjing Chen, and Hengjun Huang, and Rui Zhang, and Changxu Chen, and Kong-Peng Lam, and Shengli Xu, and Xijun Ou
Harbin Institute of Technology, Harbin 150001, China; Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China.

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.

UI MeSH Term Description Entries
D005803 Genes, Immunoglobulin Genes encoding the different subunits of the IMMUNOGLOBULINS, for example the IMMUNOGLOBULIN LIGHT CHAIN GENES and the IMMUNOGLOBULIN HEAVY CHAIN GENES. The heavy and light immunoglobulin genes are present as gene segments in the germline cells. The completed genes are created when the segments are shuffled and assembled (B-LYMPHOCYTE GENE REARRANGEMENT) during B-LYMPHOCYTE maturation. The gene segments of the human light and heavy chain germline genes are symbolized V (variable), J (joining) and C (constant). The heavy chain germline genes have an additional segment D (diversity). Genes, Ig,Immunoglobulin Genes,Gene, Ig,Gene, Immunoglobulin,Ig Gene,Ig Genes,Immunoglobulin Gene
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001402 B-Lymphocytes Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B-Cells, Lymphocyte,B-Lymphocyte,Bursa-Dependent Lymphocytes,B Cells, Lymphocyte,B Lymphocyte,B Lymphocytes,B-Cell, Lymphocyte,Bursa Dependent Lymphocytes,Bursa-Dependent Lymphocyte,Lymphocyte B-Cell,Lymphocyte B-Cells,Lymphocyte, Bursa-Dependent,Lymphocytes, Bursa-Dependent
D012322 RNA Precursors RNA transcripts of the DNA that are in some unfinished stage of post-transcriptional processing (RNA PROCESSING, POST-TRANSCRIPTIONAL) required for function. RNA precursors may undergo several steps of RNA SPLICING during which the phosphodiester bonds at exon-intron boundaries are cleaved and the introns are excised. Consequently a new bond is formed between the ends of the exons. Resulting mature RNAs can then be used; for example, mature mRNA (RNA, MESSENGER) is used as a template for protein production. Precursor RNA,Primary RNA Transcript,RNA, Messenger, Precursors,RNA, Ribosomal, Precursors,RNA, Small Nuclear, Precursors,RNA, Transfer, Precursors,Pre-mRNA,Pre-rRNA,Pre-snRNA,Pre-tRNA,Primary Transcript, RNA,RNA Precursor,mRNA Precursor,rRNA Precursor,snRNA Precursor,tRNA Precursor,Pre mRNA,Pre rRNA,Pre snRNA,Pre tRNA,Precursor, RNA,Precursor, mRNA,Precursor, rRNA,Precursor, snRNA,Precursor, tRNA,Precursors, RNA,RNA Primary Transcript,RNA Transcript, Primary,RNA, Precursor,Transcript, Primary RNA,Transcript, RNA Primary
D017381 Spliceosomes Organelles in which the splicing and excision reactions that remove introns from precursor messenger RNA molecules occur. One component of a spliceosome is five small nuclear RNA molecules (U1, U2, U4, U5, U6) that, working in conjunction with proteins, help to fold pieces of RNA into the right shapes and later splice them into the message. Spliceosome
D017414 Ribonucleoprotein, U4-U6 Small Nuclear A nuclear RNA-protein complex that plays a role in RNA processing. In the nucleoplasm, the U4-U6 snRNP along with the U5 snRNP preassemble into a single 25S particle that binds to the U1 and U2 snRNPs and the substrate to form mature SPLICEOSOMES. There is also evidence for the existence of individual U4 or U6 snRNPs in addition to their organization as a U4-U6 snRNP. Ribonucleoproteins, U4 Small Nuclear,Ribonucleoproteins, U6 Small Nuclear,Small Nuclear Ribonucleoproteins, U4,Small Nuclear Ribonucleoproteins, U4-U6,Small Nuclear Ribonucleoproteins, U6,U4 Small Nuclear Ribonucleoproteins,U4 snRNP,U4-U6 Small Nuclear Ribonucleoproteins,U4-U6 snRNP,U6 Small Nuclear Ribonucleoproteins,U6 snRNP,Ribonucleoproteins, Small, U4-U6,Ribonucleoprotein, U4 U6 Small Nuclear,Small Nuclear Ribonucleoproteins, U4 U6,U4 U6 Small Nuclear Ribonucleoproteins
D017415 Ribonucleoprotein, U5 Small Nuclear A nuclear RNA-protein complex that plays a role in RNA processing. In the nucleoplasm, the U5 snRNP along with U4-U6 snRNP preassemble into a single 25S particle that binds to the U1 and U2 snRNPs and the substrate to form SPLICEOSOMES. Small Nuclear Ribonucleoproteins, U5,U5 Small Nuclear Ribonucleoproteins,U5 snRNP,Ribonucleoproteins, Small, U5
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D064570 Ubiquitin-Specific Proteases Members of the peptidase C19 family which regulate signal transduction by removing UBIQUITIN from specific protein substrates via a process known as deubiquitination or deubiquitylation. Ubiquitin-Specific Peptidase,Ubiquitin-Specific Protease,Ubiquitin-Specific Peptidases,Ubiquitin-Specific Protease Family,Peptidase, Ubiquitin-Specific,Peptidases, Ubiquitin-Specific,Protease Family, Ubiquitin-Specific,Protease, Ubiquitin-Specific,Proteases, Ubiquitin-Specific,Ubiquitin Specific Peptidase,Ubiquitin Specific Peptidases,Ubiquitin Specific Protease,Ubiquitin Specific Protease Family,Ubiquitin Specific Proteases

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