The microprocessor component, DGCR8, is essential for early B-cell development in mice
Autor: | Sven Brenner, Hans-Martin Jäck, Andreas Brandl, Jürgen Wittmann, Desmond Y H Yap, Sebastian R. Schulz, Michael R. Bösl, Patrick Daum, Wolfgang Schuh |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
DGCR8 Immunology Cell Line Microprocessor complex 03 medical and health sciences Mice microRNA medicine Immunology and Allergy Animals Humans Ribonuclease III Progenitor cell RNA Processing Post-Transcriptional B cell Drosha Sequence Deletion B-Lymphocytes biology Precursor Cells B-Lymphoid RNA-Binding Proteins Cell Differentiation Cell biology MicroRNAs 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation biology.protein Dicer |
Zdroj: | European journal of immunology. 46(12) |
ISSN: | 1521-4141 |
Popis: | microRNAs (miRNAs) are important posttranscriptional regulators during hematopoietic lineage commitment and lymphocyte development. Mature miRNAs are processed from primary miRNA transcripts in two steps by the microprocessor complex, consisting of Drosha and its partner DiGeorge Critical Region 8 (DGCR8), and the RNAse III enzyme, Dicer. Conditional ablations of Drosha and Dicer have established the importance of both RNAses in B- and T-cell development. Here, we show that a cre-mediated B-cell specific deletion of DGCR8 in mice results in a nearly complete maturation block at the transition from the pro-B to the pre-B cell stage, and a failure to upregulate Ig μ heavy chain expression in pro-B cells. Furthermore, we found that the death of freshly isolated DGCR8-deficient pro-B cells could be partially prevented by enforced Bcl2 expression. We conclude from these findings that the microprocessor component DGCR8 is essential for survival and differentiation of early B-cell progenitors. |
Databáze: | OpenAIRE |
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