Abstract
Regulated expression of miRNAs influences development in a wide variety of contexts. We report here that miR290-5p (100049710) and miR292-5p (100049711) are induced at the pre-B stage of murine B cell development and that they influence assembly of the Igκ light chain gene (243469) by contributing to the activation of germline Igκ transcription (κGT). We found that upon forced over-expression of miR290-5p/292-5p in Abelson Murine Leukemia Virus (AMuLV) transformed pro-B cells, two known activators of κGT, E2A (21423) and NF-κB (19697), show increased chromosomal binding to the kappa intronic enhancer. Conversely, knockdown of miR290-5p/292-5p in AMuLV pro-B cells blunts drug-induced activation of κGT. Furthermore, miR290-5p/292-5p knockdown also diminishes κGT activation, but not Rag1/2 (19373, 19374) expression, in an IL-7 dependent primary pro-B cell culture system. In addition, we identified a deficiency in κGT induction in miR290 cluster knockout mice. We hypothesize that increased expression of miR290-5p and miR292-5p contributes to the induction of κGT at the pre-B stage of B cell development through increased binding of NF-κB and E2A to kappa locus regulatory sequences.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Abelson murine leukemia virus / physiology
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Animals
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B-Lymphocytes / cytology*
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B-Lymphocytes / drug effects
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B-Lymphocytes / metabolism*
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B-Lymphocytes / virology
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Benzamides
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Cell Differentiation / drug effects
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Cell Differentiation / genetics
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Cell Transformation, Viral / drug effects
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Cell Transformation, Viral / genetics
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DNA / metabolism
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / genetics
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Gene Knockdown Techniques
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Genetic Loci / genetics*
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Imatinib Mesylate
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Immunoglobulin kappa-Chains / genetics*
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Introns / genetics
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Mice
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MicroRNAs / genetics
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MicroRNAs / metabolism*
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NF-kappa B / metabolism
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Piperazines / pharmacology
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Pyrimidines / pharmacology
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Transcription, Genetic / drug effects
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Transcription, Genetic / genetics
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Benzamides
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Immunoglobulin kappa-Chains
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MIRN290 microRNA, mouse
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MIRN292 microRNA, mouse
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MicroRNAs
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NF-kappa B
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Piperazines
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Pyrimidines
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RNA, Messenger
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Tcf3 protein, mouse
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Imatinib Mesylate
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DNA