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

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-IL1 alpha, which is partially complementary to IL-1 alpha. Similar to IL-1 alpha, AS-IL1 alpha is expressed at low levels in resting macrophages and is induced following infection with Listeria monocytogenes or stimulation with TLR ligands (Pam(3)CSK(4), LPS, polyinosinic-polycytidylic acid). Inducible expression of IL-1 alpha mRNA and protein were significantly reduced in macrophages expressing shRNA that target AS-IL1 alpha. AS-IL1 alpha is located in the nucleus and did not alter the stability of IL-1 alpha mRNA. Instead, AS-IL1 alpha was required for the recruitment of RNA polymerase II to the IL-1 alpha promoter. In summary, our studies identify AS-IL1 alpha as an important regulator of IL-1 alpha transcription during the innate immune response.