TY - JOUR TI - A mammalian pseudogene lncRNA at the interface of inflammation and anti-inflammatory therapeutics AU - Rapicavoli, Nicole A AU - Qu, Kun AU - Zhang, Jiajing AU - Mikhail, Megan AU - Laberge, Remi-Martin AU - Chang, Howard Y A2 - Gingeras, Thomas VL - 2 PY - 2013 DA - 2013/07/23 SP - e00762 C1 - eLife 2013;2:e00762 DO - 10.7554/eLife.00762 UR - https://doi.org/10.7554/eLife.00762 AB - Pseudogenes are thought to be inactive gene sequences, but recent evidence of extensive pseudogene transcription raised the question of potential function. Here we discover and characterize the sets of mouse lncRNAs induced by inflammatory signaling via TNFα. TNFα regulates hundreds of lncRNAs, including 54 pseudogene lncRNAs, several of which show exquisitely selective expression in response to specific cytokines and microbial components in a NF-κB-dependent manner. Lethe, a pseudogene lncRNA, is selectively induced by proinflammatory cytokines via NF-κB or glucocorticoid receptor agonist, and functions in negative feedback signaling to NF-κB. Lethe interacts with NF-κB subunit RelA to inhibit RelA DNA binding and target gene activation. Lethe level decreases with organismal age, a physiological state associated with increased NF-κB activity. These findings suggest that expression of pseudogenes lncRNAs are actively regulated and constitute functional regulators of inflammatory signaling. KW - noncoding RNA KW - NF-κB KW - genomic JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -