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Genes Immun. 2015 Jan-Feb;16(1):89-98. doi: 10.1038/gene.2014.65. Epub 2014 Nov 20.

Human natural killer cell microRNA: differential expression of MIR181A1B1 and MIR181A2B2 genes encoding identical mature microRNAs.

Author information

1
Departments of Pathology and Laboratory Medicine, University of Kentucky Lexington, Kentucky, USA.
2
Division of Hematology, Oncology, and Transplantation, University of Minnesota Cancer Center, Minneapolis, Minnesota, USA.
3
Departments of Microbiology, Immunology, and Molecular Genetics, University of Kentucky Lexington, Kentucky, USA.
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Contributed equally

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.

PMID:
25410655
PMCID:
PMC4304976
DOI:
10.1038/gene.2014.65
[Indexed for MEDLINE]
Free PMC Article

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