Abstract
Killer Ig-like receptors (KIRs) are expressed in a variegated, clonally restricted fashion on NK cells and are important determinants of NK cell function. Although silencing of individual KIR genes is strongly correlated with the presence of CpG dinucleotide methylation within the promoter, the mechanism responsible for silencing has not been identified. Our results show that antisense transcripts mediate KIR transcriptional silencing through a novel PIWI-like 28-base small RNA. Although PIWI RNA-mediated silencing of transposable elements within germ cells have been described, this is the first report that identifies a PIWI-like RNA in an immune somatic cell lineage and identifies a mechanism that may be broadly used in orchestrating immune development.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
MeSH terms
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Argonaute Proteins
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Base Sequence
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Blotting, Western
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Cell Line
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Cells, Cultured
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CpG Islands / genetics
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DNA Methylation
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Flow Cytometry
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Gene Expression Profiling
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Genetic Vectors / genetics
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Humans
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Killer Cells, Natural / cytology
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Killer Cells, Natural / metabolism*
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Lentivirus / genetics
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Molecular Sequence Data
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Promoter Regions, Genetic / genetics
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Proteins / genetics*
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Proteins / metabolism
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RNA / genetics
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RNA / metabolism*
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RNA, Antisense / genetics
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RNA, Antisense / metabolism*
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RNA-Binding Proteins
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Receptors, KIR3DL1 / genetics*
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Receptors, KIR3DL1 / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Sequence Homology, Nucleic Acid
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Transcription, Genetic
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Transduction, Genetic
Substances
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Argonaute Proteins
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KIR3DL1 protein, human
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PIWIL4 protein, human
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Proteins
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RNA, Antisense
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RNA-Binding Proteins
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Receptors, KIR3DL1
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RNA