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Publication : Spliceosome component PHD finger 5A is essential for early B lymphopoiesis.

First Author  Zhang R Year  2024
Journal  Development Volume  151
Issue  2 PubMed ID  38095286
Mgi Jnum  J:345807 Mgi Id  MGI:7579255
Doi  10.1242/dev.202247 Citation  Zhang R, et al. (2024) Spliceosome component PHD finger 5A is essential for early B lymphopoiesis. Development 151(2):dev202247
abstractText  The spliceosome, a multi-megadalton ribonucleoprotein complex, is essential for pre-mRNA splicing in the nucleus and ensuring genomic stability. Its precise and dynamic assembly is pivotal for its function. Spliceosome malfunctions can lead to developmental abnormalities and potentially contribute to tumorigenesis. The specific role of the spliceosome in B cell development is poorly understood. Here, we reveal that the spliceosomal U2 snRNP component PHD finger protein 5A (Phf5a) is vital for early B cell development. Loss of Phf5a results in pronounced defects in B cell development, causing an arrest at the transition from pre-pro-B to early pro-B cell stage in the bone marrow of mutant mice. Phf5a-deficient B cells exhibit impaired immunoglobulin heavy (IgH) chain expression due to defective V-to-DJ gene rearrangement. Mechanistically, our findings suggest that Phf5a facilitates IgH gene rearrangement by regulating the activity of recombination-activating gene endonuclease and influencing chromatin interactions at the Igh locus.
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