title: miR290-5p/292-5p activate the immunoglobulin kappa locus in B cell development.
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.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, California, United States of America.
authors.forename: Patty B
authors.initials: PB
authors.lastname: Garcia
authors.forename: Amie
authors.initials: A
authors.lastname: Cai
authors.forename: Jamie G
authors.initials: JG
authors.lastname: Bates
authors.forename: Hector
authors.initials: H
authors.lastname: Nolla
authors.forename: Mark S
authors.initials: MS
authors.lastname: Schlissel
mesh_terms: D000011:Abelson murine leukemia virus / Q000502:physiology; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism* / Q000821:virology; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001549:Benzamides; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002472:Cell Transformation, Viral / Q000187:drug effects / Q000235:genetics; D004247:DNA / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D055785:Gene Knockdown Techniques; D056426:Genetic Loci / Q000235:genetics*; D000068877:Imatinib Mesylate; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D007438:Introns / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D001549:Benzamides; D004247:DNA; D000068877:Imatinib Mesylate; D007145:Immunoglobulin kappa-Chains; D035683:MicroRNAs; D016328:NF-kappa B; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; C547384:MIRN290 microRNA, mouse; C577758:MIRN292 microRNA, mouse; C075668:Tcf3 protein, mouse