Department of Molecular and Cell Biology, University of California, Berkeley, California, United States of America.
PLoS One. 2012;7(8):e43805. doi: 10.1371/journal.pone.0043805. Epub 2012 Aug 23.
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.
miRNAs 的调控表达会影响各种情况下的发育。我们在这里报告，miR290-5p（100049710）和 miR292-5p（100049711）在小鼠 B 细胞发育的前 B 期被诱导，并且它们通过促进免疫球蛋白κ轻链基因（243469）的胚系转录（κGT）来影响免疫球蛋白κ轻链基因的组装。我们发现，在 Abelson 鼠白血病病毒（AMuLV）转化的前 B 细胞中强制过表达 miR290-5p/292-5p 时，两个已知的 κGT 激活因子 E2A（21423）和 NF-κB（19697）显示出增加的染色体结合到κ内含子增强子上。相反，在 AMuLV 前 B 细胞中敲低 miR290-5p/292-5p 会削弱药物诱导的 κGT 激活。此外，在 IL-7 依赖性原代前 B 细胞培养系统中，miR290-5p/292-5p 敲低也会减弱 κGT 的激活，但不会减弱 Rag1/2（19373，19374）的表达。此外，我们还发现 miR290 簇敲除小鼠中 κGT 诱导的缺陷。我们假设 miR290-5p 和 miR292-5p 的表达增加通过增加 NF-κB 和 E2A 与 κ 基因座调控序列的结合，有助于 B 细胞发育前 B 期的 κGT 诱导。
