Journal Article

miR290-5p/292-5p Activate the Immunoglobulin kappa Locus in B Cell Development

Nolla, Hector, Schlissel, Mark S., Garcia, Patty B., Cai, Amie, Bates, Jamie G.

2012

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Abelson murine leukemia virus - physiology / Animals / B cells / B-Lymphocytes - cytology / B-Lymphocytes - drug effects / B-Lymphocytes - metabolism / B-Lymphocytes - virology / Basic Helix-Loop-Helix Transcription Factors - metabolism / Benzamides / Binding / Biology / Cell activation / Cell culture / Cell cycle / Cell Differentiation - drug effects / Cell Differentiation - genetics / Cell Transformation, Viral - drug effects / Cell Transformation, Viral - genetics / Developmental stages / DNA - metabolism / DNA methylation / Enzymes / Gene expression / Gene Expression Regulation - drug effects / Gene Expression Regulation - genetics / Gene Knockdown Techniques / Genetic aspects / Genetic Loci - genetics / Genomics / Imatinib Mesylate / Immunoglobulin kappa-Chains - genetics / Immunoglobulins / Interleukin 7 / Introns - genetics / Kinases / Leukemia / Loci / Lymphocytes B / Mice / MicroRNA / MicroRNAs / MicroRNAs - genetics / MicroRNAs - metabolism / NF-kappa B - metabolism / NF-κB protein / Overexpression / Piperazines - pharmacology / Pyrimidines - pharmacology / RAG1 protein / Regulatory sequences / RNA, Messenger - genetics / RNA, Messenger - metabolism / Stem cells / Studies / Transcription (Genetics) / Transcription activation / Transcription factors / Transcription, Genetic - drug effects / Transcription, Genetic - genetics / Viruses