Cutting Edge: A Natural Antisense Transcript, AS-IL1α, Controls Inducible Transcription of the Proinflammatory Cytokine IL-1α.

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Journal of immunology (Baltimore, Md. : 1950), ISSN: 1550-6606, Vol: 195, Issue: 4, Page: 1359-63

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Chan, Jennie; Atianand, Maninjay K.; Jiang, Zhaozhao; Carpenter, Susan B.; Aiello, Daniel; Elling, Roland; Fitzgerald, Katherine A.; Caffrey, Daniel R.
The American Association of Immunologists
Immunology and Microbiology; Animals; Cell Line; Cluster Analysis; Gene Expression Profiling; *Gene Expression Regulation; Gene Knockdown Techniques; Genetic Loci; *Inflammation Mediators; Interleukin-1alpha; Ligands; Macrophages; Mice; NF-kappa B; RNA Interference; RNA, Antisense; RNA, Untranslated; Toll-Like Receptors; *Transcription, Genetic; Immunity
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Natural antisense transcripts (NATs) are a class of long noncoding RNAs (lncRNAs) that are complementary to other protein-coding genes. Although thousands of NATs are encoded by mammalian genomes, their functions in innate immunity are unknown. In this study, we identified and characterized a novel NAT, AS-IL1α, which is partially complementary to IL-1α. Similar to IL-1α, AS-IL1α is expressed at low levels in resting macrophages and is induced following infection with Listeria monocytogenes or stimulation with TLR ligands (Pam3CSK4, LPS, polyinosinic-polycytidylic acid). Inducible expression of IL-1α mRNA and protein were significantly reduced in macrophages expressing shRNA that target AS-IL1α. AS-IL1α is located in the nucleus and did not alter the stability of IL-1α mRNA. Instead, AS-IL1α was required for the recruitment of RNA polymerase II to the IL-1α promoter. In summary, our studies identify AS-IL1α as an important regulator of IL-1α transcription during the innate immune response.