A mammalian pseudogene lncRNA at the interface of inflammation and anti-inflammatory therapeutics
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, incl...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2013-07-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/00762 |
| _version_ | 1811180600820760576 |
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| author | Nicole A Rapicavoli Kun Qu Jiajing Zhang Megan Mikhail Remi-Martin Laberge Howard Y Chang |
| author_facet | Nicole A Rapicavoli Kun Qu Jiajing Zhang Megan Mikhail Remi-Martin Laberge Howard Y Chang |
| author_sort | Nicole A Rapicavoli |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T09:06:05Z |
| format | Article |
| id | doaj.art-5770f67f0e574668857d86e2494269ad |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:06:05Z |
| publishDate | 2013-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-5770f67f0e574668857d86e2494269ad2022-12-22T04:32:37ZengeLife Sciences Publications LtdeLife2050-084X2013-07-01210.7554/eLife.00762A mammalian pseudogene lncRNA at the interface of inflammation and anti-inflammatory therapeuticsNicole A Rapicavoli0Kun Qu1Jiajing Zhang2Megan Mikhail3Remi-Martin Laberge4Howard Y Chang5Program in Epithelial Biology, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, United StatesProgram in Epithelial Biology, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, United StatesProgram in Epithelial Biology, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, United StatesProgram in Epithelial Biology, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, United StatesBuck Institute for Research on Aging, Novato, United StatesProgram in Epithelial Biology, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, United StatesPseudogenes 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.https://elifesciences.org/articles/00762noncoding RNANF-κBgenomic |
| spellingShingle | Nicole A Rapicavoli Kun Qu Jiajing Zhang Megan Mikhail Remi-Martin Laberge Howard Y Chang A mammalian pseudogene lncRNA at the interface of inflammation and anti-inflammatory therapeutics eLife noncoding RNA NF-κB genomic |
| title | A mammalian pseudogene lncRNA at the interface of inflammation and anti-inflammatory therapeutics |
| title_full | A mammalian pseudogene lncRNA at the interface of inflammation and anti-inflammatory therapeutics |
| title_fullStr | A mammalian pseudogene lncRNA at the interface of inflammation and anti-inflammatory therapeutics |
| title_full_unstemmed | A mammalian pseudogene lncRNA at the interface of inflammation and anti-inflammatory therapeutics |
| title_short | A mammalian pseudogene lncRNA at the interface of inflammation and anti-inflammatory therapeutics |
| title_sort | mammalian pseudogene lncrna at the interface of inflammation and anti inflammatory therapeutics |
| topic | noncoding RNA NF-κB genomic |
| url | https://elifesciences.org/articles/00762 |
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