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A pseudogene lncRNA at the interface of inflammation and anti-inflammatory therapeutics

GSE47494 Mus musculus Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing 6 samples Submitted 2013/08/05 Platform GPL9250
Summary
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 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.
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Also filed as BioProject PRJNA205994 and SRA study SRP023473. Searching any of these in the dataset finder brings you back here.

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