Cutting Edge: A Natural Antisense Transcript, AS-IL1alpha, Controls Inducible Transcription of the Proinflammatory Cytokine IL-1alpha
Program in Innate Immunity; Department of Medicine, Division of Infectious Diseases and Immunology
Medical Subject Headings
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
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-IL1alpha, which is partially complementary to IL-1alpha. Similar to IL-1alpha, AS-IL1alpha 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-1alpha mRNA and protein were significantly reduced in macrophages expressing shRNA that target AS-IL1alpha. AS-IL1alpha is located in the nucleus and did not alter the stability of IL-1alpha mRNA. Instead, AS-IL1alpha was required for the recruitment of RNA polymerase II to the IL-1alpha promoter. In summary, our studies identify AS-IL1alpha as an important regulator of IL-1alpha transcription during the innate immune response.
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Citation: J Immunol. 2015 Aug 15;195(4):1359-63. doi: 10.4049/jimmunol.1500264. Epub 2015 Jul 15. Link to article on publisher's site
Chan, Jennie; Atianand, Maninjay K.; Jiang, Zhaozhao; Carpenter, Susan B.; Aiello, Daniel; Elling, Roland; Fitzgerald, Katherine A.; and Caffrey, Daniel R., "Cutting Edge: A Natural Antisense Transcript, AS-IL1alpha, Controls Inducible Transcription of the Proinflammatory Cytokine IL-1alpha" (2015). University of Massachusetts Medical School Faculty Publications. 944.