title: Human natural killer cell microRNA: differential expression of MIR181A1B1 and MIR181A2B2 genes encoding identical mature microRNAs.
abstract: Natural killer (NK) and T lymphocytes share many properties, yet only NK cells respond rapidly to infection and cancer without pre-activation. We found that few microRNAs (miRNAs) differed significantly between human NK and T cells. Among those miRNAs, miR-181a and miR-181b levels rose during NK cell differentiation. Prior studies indicate that miR-181a and miR-181b are critical for human NK cell development and are co-transcribed from genes on chromosome 1 (MIR181A1B1) and on chromosome 9 (MIR181A2B2). We mapped human MIR181A1B1 and MIR181A2B2 transcription start sites to 78.3 kb and 34.0 kb upstream of the mature miRNAs, generating predominantly unspliced transcripts of 80-127 kb and ~60 kb, respectively. Unlike mouse thymocytes, human T cells expressed both MIR181A1B1 and MIR181A2B2. We tested the hypothesis that NK cells differentially transcribe the two genes during development and in response to immune regulatory cytokines. During NK-cell differentiation, MIR181A2B2 expression rose markedly and exceeded that of MIR181A1B1. TGF-β treatment increased NK-cell MIR181A2B2 transcription, whereas IL-2, IL-15 and IL-12/IL-18 treatments upregulated MIR181A1B1. The MIR181A2B2 promoter was strongly transactivated by SMAD3 and SMAD4 transcription factors, suggesting that TGF-β signaling upregulates MIR181A2B2 expression, at least in part, through SMAD-dependent promoter activation.
authors.affiliation: Departments of Pathology and Laboratory Medicine, University of Kentucky Lexington, Kentucky, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Presnell
authors.affiliation: Departments of Pathology and Laboratory Medicine, University of Kentucky Lexington, Kentucky, USA.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Al-Attar
authors.affiliation: Division of Hematology, Oncology, and Transplantation, University of Minnesota Cancer Center, Minneapolis, Minnesota, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Cichocki
authors.affiliation: Division of Hematology, Oncology, and Transplantation, University of Minnesota Cancer Center, Minneapolis, Minnesota, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Miller
authors.affiliation: Departments of Pathology and Laboratory Medicine, University of Kentucky Lexington, Kentucky, USA.|Departments of Microbiology, Immunology, and Molecular Genetics, University of Kentucky Lexington, Kentucky, USA.
authors.forename: Charles T
authors.initials: CT
authors.lastname: Lutz
mesh_terms: D015870:Gene Expression; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D011401:Promoter Regions, Genetic; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D024363:Transcription Initiation Site
chemical_list: C540193:MIrn181 microRNA, human; D035683:MicroRNAs