title: Identification of a KIR antisense lncRNA expressed by progenitor cells.
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.
authors.affiliation: Lab of Experimental Immunology, SAIC-Frederick Inc., Frederick National Lab, Frederick, MD, USA.
authors.forename: P W
authors.initials: PW
authors.lastname: Wright
authors.forename: A
authors.initials: A
authors.lastname: Huehn
authors.forename: F
authors.initials: F
authors.lastname: Cichocki
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: N
authors.initials: N
authors.lastname: Sharma
authors.forename: H
authors.initials: H
authors.lastname: Dang
authors.forename: T R
authors.initials: TR
authors.lastname: Lenvik
authors.forename: P
authors.initials: P
authors.lastname: Woll
authors.forename: D
authors.initials: D
authors.lastname: Kaufman
authors.forename: J S
authors.initials: JS
authors.lastname: Miller
authors.forename: S K
authors.initials: SK
authors.lastname: Anderson
mesh_terms: D001665:Binding Sites; D053595:Embryonic Stem Cells / Q000378:metabolism*; D005091:Exons; D020868:Gene Silencing; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007438:Introns; D051741:Kruppel-Like Transcription Factors / Q000737:chemistry / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D016372:RNA, Antisense / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D054340:Receptors, KIR / Q000235:genetics* / Q000378:metabolism
chemical_list: D051741:Kruppel-Like Transcription Factors; C085969:MZF1 protein, human; D016372:RNA, Antisense; D062085:RNA, Long Noncoding; D054340:Receptors, KIR