[Show abstract][Hide abstract] ABSTRACT: Human NK cells express cell surface class I MHC receptors (killer cell immunoglobulin-like receptor, KIR) in a probabilistic manner. Previous studies have shown that a distal promoter acts in conjunction with a proximal bidirectional promoter to control the selective activation of KIR genes. We report here the presence of an intron 2 promoter in several KIR genes that produce a spliced antisense transcript. This long noncoding RNA (lncRNA) transcript contains antisense sequence complementary to KIR-coding exons 1 and 2 as well as the proximal promoter region of the KIR genes. The antisense promoter contains myeloid zinc finger 1 (MZF-1)-binding sites, a transcription factor found in hematopoietic progenitors and myeloid precursors. The KIR antisense lncRNA was detected only in progenitor cells or pluripotent cell lines, suggesting a function that is specific for stem cells. Overexpression of MZF-1 in developing NK cells led to decreased KIR expression, consistent with a role for the KIR antisense lncRNA in silencing KIR gene expression early in development.Genes and Immunity advance online publication, 18 July 2013; doi:10.1038/gene.2013.36.
Genes and immunity 07/2013; 14(7). DOI:10.1038/gene.2013.36 · 2.91 Impact Factor
[Show abstract][Hide abstract] 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.
The Journal of Immunology 08/2010; 185(4):2009-12. DOI:10.4049/jimmunol.1000855 · 4.92 Impact Factor