The spliceosome component Usp39 controls B cell development by regulating immunoglobulin gene rearrangement.
Cell Rep
; 38(6): 110338, 2022 02 08.
Article
en En
| MEDLINE
| ID: mdl-35139388
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Genes de Inmunoglobulinas
/
Precursores del ARN
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Linfocitos B
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Empalmosomas
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Proteasas Ubiquitina-Específicas
Límite:
Animals
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Humans
Idioma:
En
Revista:
Cell Rep
Año:
2022
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA