Unknown,Transcriptomics,Genomics,Proteomics

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Long non-coding RNAs act as novel mediators of Innate Immunity

ABSTRACT: Recent advances in genome technologies have uncovered thousands of long non-coding RNAs (lncRNAs) whose function in the immune system has been largely unexplored. Members of the Toll-like receptor (TLR) family activate an inducible program of inflammatory genes important in host defenses. Here we provide evidence that TLRs induce the expression of many lncRNAs. One of these (lncRNA-Cox2) modulates the expression of hundreds of TLR2-inducible genes. Functional studies identified this lncRNA as capable of both activation and repression of distinct groups of TLR-induced genes. Transcriptional repression mediated by lncRNA-Cox2 requires heterogeneous ribonucleoprotein A/B and A2/B1, binding partners for lncRNA-Cox2. Collectively, these studies identify lncRNA-Cox2 as a broad-acting component of the regulatory circuit that controls the TLR-induced inflammatory response. Examination of Mus musculus (C57BL/6 background) gene exression changes following stimulation with Pam3Cys4 in presence or absence of shRNA specifically targetting lncRNA-COX2

ORGANISM(S): Mus musculus

SUBMITTER: Daniel Aiello

PROVIDER: E-GEOD-40978 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

A long noncoding RNA mediates both activation and repression of immune response genes.

Carpenter Susan S Aiello Daniel D Atianand Maninjay K MK Ricci Emiliano P EP Gandhi Pallavi P Hall Lisa L LL Byron Meg M Monks Brian B Henry-Bezy Meabh M Lawrence Jeanne B JB O'Neill Luke A J LA Moore Melissa J MJ Caffrey Daniel R DR Fitzgerald Katherine A KA

Science (New York, N.Y.) 20130801 6147

An inducible program of inflammatory gene expression is central to antimicrobial defenses. This response is controlled by a collaboration involving signal-dependent activation of transcription factors, transcriptional co-regulators, and chromatin-modifying factors. We have identified a long noncoding RNA (lncRNA) that acts as a key regulator of this inflammatory response. Pattern recognition receptors such as the Toll-like receptors induce the expression of numerous lncRNAs. One of these, lincRN ...[more]

PMID: 23907535

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Project description:We aimed at systematically inferring the regulatory functions of host lncRNAs in response to influenza A virus (IAV) and severe acute respiratory syndrome coronavirus (SARS-CoV) in the mouse model, using a ‘guilt-by-association’ approach which relies on finding which lncRNAs have similar expression profiles to protein-coding genes of known function. To build a large panel of diverse host responses to viral infection, we took advantage of the genetic diversity present in the 8 founder strains of the Collaborative Cross (CC) mouse resource. Extensive pulmonary host-response profiling was performed on mock and viral-infected lungs at 2 and 4 days post-infection using total RNA-Seq. Overall lncRNAs accounted for about 40% of total genes differentially expressed upon infections (5,329 DE lncRNAs). To predict the functions of these lncRNAs, we constructed a co-expression network using the weighted correlation network analysis (WGCNA) and identified modules of co-expressed genes. Several lncRNAs were identified as belonging to gene modules associated with viral replication or weight loss, and enriched in various infection-related biological processes such as immune response. In addition, each lncRNA was individually annotated using ranked list of DE genes based on signed correlation with each LncRNA. We predicted that a few lncRNAs may be implicated in more than 50 biological processes or pathways. Finally, we identified the lncRNAs that were positively or negatively correlated with all their neighbors and may have cis enhancer or inhibitor effects. We validated our prediction by examining additional RNASeq dataset of mice treated with IFN-alpha. Altogether, these results provide a broad categorization of lncRNA functions and identify subsets of lncRNAs with potential key roles for respiratory virus pathogenesis. These data are fully accessible through The MOuse NOn-Code Lung database (MONOCLdb) http://monocldb.viromics.washington.edu/ At 2 or 4 days post infection, Collaborative Cross founders mice (n=2-3 for infected conditions, n=2 for mocks) were euthanized and lungs were used for total RNA-Seq.

Dataset Information

Long non-coding RNAs act as novel mediators of Innate Immunity

Publications

A long noncoding RNA mediates both activation and repression of immune response genes.

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