title: The microprocessor component, DGCR8, is essential for early B-cell development in mice.
abstract: 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.
authors.affiliation: Division of Molecular Immunology, Internal Medicine III, Nikolaus-Fiebiger-Center of Molecular Medicine, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Brandl
authors.affiliation: Division of Molecular Immunology, Internal Medicine III, Nikolaus-Fiebiger-Center of Molecular Medicine, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Daum
authors.affiliation: Department of Genetics, Friedrich-Alexander University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Brenner
authors.affiliation: Division of Molecular Immunology, Internal Medicine III, Nikolaus-Fiebiger-Center of Molecular Medicine, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Sebastian R
authors.initials: SR
authors.lastname: Schulz
authors.affiliation: Division of Molecular Immunology, Internal Medicine III, Nikolaus-Fiebiger-Center of Molecular Medicine, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Desmond Yat-Hin
authors.initials: DY
authors.lastname: Yap
authors.affiliation: Institute of Experimental Biomedicine, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bösl
authors.affiliation: Division of Molecular Immunology, Internal Medicine III, Nikolaus-Fiebiger-Center of Molecular Medicine, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wittmann
authors.affiliation: Division of Molecular Immunology, Internal Medicine III, Nikolaus-Fiebiger-Center of Molecular Medicine, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schuh
authors.affiliation: Division of Molecular Immunology, Internal Medicine III, Nikolaus-Fiebiger-Center of Molecular Medicine, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Jäck
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics; D054448:Precursor Cells, B-Lymphoid / Q000502:physiology*; D012323:RNA Processing, Post-Transcriptional; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion / Q000235:genetics
chemical_list: C474044:Dgcr8 protein, mouse; D035683:MicroRNAs; D016601:RNA-Binding Proteins
keywords: B cells · DGCR8 · Drosha · microRNA · pre-BCR