Dataset Information

Temporal analysis of RNA turnover in Interferon Gamma treated bone marrow-derived macrophages

ABSTRACT: Interferon gamma treatment of macrophages results in hundreds if not thousands of alterations in gene expression and an antiviral state being established in these cells. Little is known about relationship between transcript synthesis, abundance and decay in macrophages during the first hours after interferon gamma treatment and how these factors influence the antiviral cellular phenotype. Microarrays were used to analyse alterations in transcript synthesis and abundance in BMDM treated with Interferon Gamma for 8h.

ORGANISM(S): Mus musculus

PROVIDER: GSE63290 | GEO | 2016/03/07

SECONDARY ACCESSION(S): PRJNA267204

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:The goal of this analysis was to utilize microarray profiling to identify basal alterations in gene expression in response to TFAM depletion and mtDNA stress. Mitochondrial DNA (mtDNA) is normally present at thousands of copies per cell and is packaged into several hundred higher-order structures termed nucleoids. The abundant mtDNA-binding protein, TFAM (transcription factor A,mitochondrial), regulates nucleoid architecture, abundance and segregation. Complete mtDNA depletion profoundly impairs oxidative phosphorylation, triggering calcium-dependent stress signalling and adaptive metabolic responses. However, the cellular responses to mtDNA instability, a physiologically relevant stress observed in many human diseases and ageing, remain poorly defined. Here we show that moderate mtDNA stress elicited by TFAM deficiency engages cytosolic antiviral signalling to enhance the expression of a subset of interferon-stimulated genes. Mechanistically, we find that aberrant mtDNA packaging promotes escape of mtDNA into the cytosol, where it engages the DNA sensor cGAS (also known as MB21D1) and promotes STING (also known as TMEM173)–IRF3-dependent signalling to elevate interferon-stimulated gene expression, potentiate type I interferon responses and confer broad viral resistance. Furthermore, we demonstrate that herpesviruses induce mtDNA stress, which enhances antiviral signalling and type I interferon responses during infection. Our results further demonstrate that mitochondria are central participants in innate immunity, identify mtDNA stress as a cell-intrinsic trigger of antiviral signaling and suggest that cellular monitoring of mtDNA homeostasis cooperates with canonical virus sensing mechanisms to fully engage antiviral innate immunity. Murine embryonic fibroblasts were isolated from wild-type or Tfam+/- E13.5 littermate embryos. RNA from passage-matched wild-type and Tfam+/- MEF lines was extracted in duplicate and hybridized onto Affymetrix microarrays. Four arrays were performed in total with two technical replicates per genotype.

Dataset Information

Temporal analysis of RNA turnover in Interferon Gamma treated bone marrow-derived macrophages

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure