Identification of a KIR antisense lncRNA expressed by progenitor cells

P. W. Wright, A. Huehn, F. Cichocki, H. Li, N. Sharma, H. Dang, T. R. Lenvik, P. Woll, D. Kaufman, J. S. Miller, S. K. Anderson

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)427-433
Number of pages7
JournalGenes and Immunity
Volume14
Issue number7
DOIs
StatePublished - 2013

Bibliographical note

Funding Information:
This project has been funded in whole or in part with federal funds from the National Cancer Institute (NCI), NIH, under contract HHSN261200800001E and NCI grant P01 111412 (JSM, SKA). This research was supported in part by the Intramural Research Program of the NIH, NCI, Center for Cancer Research.

Keywords

  • KIR
  • antisense
  • human NK cells
  • lncRNA
  • transcription

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