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

Chan, Jennie; Atianand, Maninjay K.; Jiang, Zhaozhao; Carpenter, Susan; Aiello, Daniel; Elling, Roland; Fitzgerald, Katherine A.; Caffrey, Daniel R.

doi:10.4049/jimmunol.1500264

Cited by 100 publications

(95 citation statements)

References 19 publications

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“…Indeed, lncRNAs are differentially regulated in virus-infected cells (45) and in dendritic cells or macrophages following stimulation by ligands for TLR4 (LPS) and TLR2 (Pam3CSK4) (22,26,27). Through NF-B signaling, lincRNA-Cox2, AS-IL1␣, and PACER (p50-associated COX-2 extragenic RNA) are up-regulated in macrophages upon ligation of numerous TLRs, including TLR4 by LPS (26,46,47). Similarly, IL1␤-eRNA, IL1␤-RBT46, and lnc13 are induced in human monocytes and macrophages in response to LPS through NF-B signaling (48,49).…”

Section: Lncrnas Models Of Transcriptional Control and Expression Inmentioning

confidence: 99%

“…This sequestration promotes the formation and binding of NF-B p50-p65 heterodimers to activate PTGS2 transcription. In response to Listeria monocytogenes infection and TLR1-4 activation, AS-IL-1␣ is highly up-regulated through NF-B signaling (47). AS-IL-1␣ is required for the inducible expression of IL-1␣.…”

Section: Lncrnas As Enhancers Of the Inflammatory Responsementioning

confidence: 99%

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Long non-coding RNAs (lncRNAs) and their transcriptional control of inflammatory responses

Mathy

Chen

2017

Journal of Biological Chemistry

211

162

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Edited by George M. Carman Long non-coding RNAs (lncRNAs) have emerged as potential key regulators of the inflammatory response, particularly by modulating the transcriptional control of inflammatory genes. lncRNAs may act as an enhancer or suppressor to inflammatory transcription, function as scaffold molecules through interactions with RNA-binding proteins in chromatin remodeling complexes, and modulate dynamic and epigenetic control of inflammatory transcription in a gene-specific and time-dependent fashion. Here, we will review recent literature regarding the role of lncRNAs in transcriptional control of inflammatory responses. Better understanding of lncRNA regulation of inflammation will provide novel targets for the development of new therapeutic strategies.Because of the potentially destructive nature of the inflammatory response, the expression of inflammation-related genes is finely regulated at multiple levels, including transcription, mRNA processing, translation, phosphorylation, and degradation. Transcription represents an essential, and often the most important, regulatory determinant of the inflammation process. Many signaling pathways and transcription factors are involved in the inflammatory response, including the transcription factor nuclear factor-B (NF-B), 2 MAPK, and JAK/ STAT pathways, together controlling a multitude of inflammatory response genes (1, 2). Upon activation, these pathways directly activate and induce the expression of a limited set of transcription factors that promote the transcription of inflammatory genes. Whereas the mechanisms of initial activation and subsequent nuclear translocation of associated transcription factors for these signaling pathways are well-characterized, how the transcription of inflammatory genes is finely controlled in the nucleus to ensure that each individual gene is transcribed at the "right" place at the "right" time remains elusive. Perhaps this can be best represented by the inflammatory transcription induced by NF-B. The NF-B signaling cascade can be activated by inflammatory signals, including LPS, TNF-␣, IL-1␤, and reactive oxygen species, among others; many Toll-like receptors (TLRs) also activate NF-B (3-8).Prior to an activating signal, NF-B dimers are sequestered in the cytoplasm and held inactive by association with I B proteins (9). Activating stimuli cause I B degradation (10, 11), and consequently, free NF-B dimers translocate to the nucleus, bind to B sites, and promote gene transcription (12). Common targets of NF-B include inflammatory cytokines, chemokines, adhesion molecules, cytoprotective proteins, and proteins regulating cell differentiation, proliferation, and survival (13,14). In addition to its initial cytoplasmic activation, both the recruitment of NF-B to target genes in the nuclei and NF-B-induced transcriptional events after recruitment are finely controlled events to ensure proper transactivation of NF-B target genes (15). Indeed, several waves of gene transcription have been demonstrated in macrophages following LP...

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Section: Lncrnas Models Of Transcriptional Control and Expression Inmentioning

confidence: 99%

Section: Lncrnas As Enhancers Of the Inflammatory Responsementioning

confidence: 99%

Long non-coding RNAs (lncRNAs) and their transcriptional control of inflammatory responses

Mathy

Chen

2017

Journal of Biological Chemistry

211

162

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“…Besides lincRNA-Cox2 and lincRNA-EPS another lncRNA called AS-IL1α has been shown to be induced after L. monocytogenes infection of mouse macrophages as well as stimulation with a range of TLR ligands (Pam3CSK4-TLR2, LPS-TLR4, polyinosinic-polycytidylic acid-TLR3) in a NFκB dependent fashion. AS-IL1α is partially complementary to IL1α and has been shown to enhance IL1α expression by recruiting RNA pol II to the IL1α promotor (Chan et al, 2015). …”

Section: Functional and Mechanistic Studiesmentioning

confidence: 99%

A Long Journey Ahead: Long Non-coding RNAs in Bacterial Infections

Bruegge

Einspanier

Sharbati

2017

Front. Cell. Infect. Microbiol.

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Bacterial pathogens have coevolved with their hosts and acquired strategies to circumvent defense mechanisms of host cells. It was shown that bacteria interfere with the expression of mammalian microRNAs to modify immune signaling, autophagy, or the apoptotic machinery. Recently, a new class of regulatory RNAs, long non-coding RNAs (lncRNAs), was reported to have a pivotal role in the regulation of eukaryotic gene expression. A growing body of literature reports on specific involvement of lncRNAs in the host cell response toward bacterial infections. This mini review summarizes recent data that focuses on lncRNA function in host cells during bacterial infection and provides a perspective where future research in this regard may be going.

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“…For example, lincRNA-Cox2 was identified as a dynamically regulated gene induced by TLR ligands that, in turn, acts to both promote and repress inflammatory gene expression (Carpenter et al, 2013). Several additional lincRNAs including THRIL (Li et al, 2014), lnc13 (Castellanos-Rubio et al, 2016) and an antisense lncRNA, AS-IL-1α (Chan et al, 2015) also regulate inflammatory gene expression in myeloid cells. In T cells, NeST regulates IFN-γ gene transcription and persistent infection with Theiler’s virus (Gomez et al, 2013), while the lncRNA Rmrp regulates effector functions of T-helper 17 cells (Huang et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

A Long Noncoding RNA lincRNA-EPS Acts as a Transcriptional Brake to Restrain Inflammation

Atianand

Satpathy

et al. 2016

Cell

Self Cite

401

360

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SUMMARY Long intergenic noncoding RNAs (lincRNA) are important regulators of gene expression. Although lincRNAs are expressed in immune cells, their functions in immunity are largely unexplored. Here we identify an immunoregulatory lincRNA, lincRNA-EPS, that is precisely regulated in macrophages to control the expression of immune response genes (IRGs). Transcriptome analysis of macrophages from lincRNA-EPS-deficient mice, combined with gain-of-function and rescue experiments, revealed a specific role for this lincRNA in restraining IRG expression. Consistently, lincRNA-EPS-deficient mice manifest enhanced inflammation and lethality following endotoxin challenge in vivo. lincRNA-EPS associates with chromatin at regulatory regions of IRGs to control nucleosome positioning and repress transcription. Further, lincRNA-EPS mediates these effects by interacting with heterogeneous nuclear ribonucleoprotein L via a CANACA motif located in its 3′ end. Together, these findings identify lincRNA-EPS as a repressor of inflammatory responses highlighting the importance of lincRNAs in the immune system.

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

Cited by 100 publications

References 19 publications

Long non-coding RNAs (lncRNAs) and their transcriptional control of inflammatory responses

Long non-coding RNAs (lncRNAs) and their transcriptional control of inflammatory responses

A Long Journey Ahead: Long Non-coding RNAs in Bacterial Infections

A Long Noncoding RNA lincRNA-EPS Acts as a Transcriptional Brake to Restrain Inflammation

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