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Telomere-to-mitochondria signaling by ZBP1 mediates replicative crisis (RIP-Seq)

ABSTRACT: Interaction between ZBP1 and TERRA-derived RNA fragments

ORGANISM(S): Homo sapiens

PROVIDER: GSE218394 | GEO | 2022/12/12

REPOSITORIES: GEO

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Telomere-to-mitochondria signalling by ZBP1 mediates replicative crisis.

Project description:Cancers arise through the accumulation of genetic and epigenetic alterations that enable cells to evade telomere-based proliferative barriers and achieve immortality. One such barrier is replicative crisis-an autophagy-dependent program that eliminates checkpoint-deficient cells with unstable telomeres and other cancer-relevant chromosomal aberrations1,2. However, little is known about the molecular events that regulate the onset of this important tumour-suppressive barrier. Here we identified the innate immune sensor Z-DNA binding protein 1 (ZBP1) as a regulator of the crisis program. A crisis-associated isoform of ZBP1 is induced by the cGAS-STING DNA-sensing pathway, but reaches full activation only when associated with telomeric-repeat-containing RNA (TERRA) transcripts that are synthesized from dysfunctional telomeres. TERRA-bound ZBP1 oligomerizes into filaments on the outer mitochondrial membrane of a subset of mitochondria, where it activates the innate immune adapter protein mitochondrial antiviral-signalling protein (MAVS). We propose that these oligomerization properties of ZBP1 serve as a signal amplification mechanism, where few TERRA-ZBP1 interactions are sufficient to launch a detrimental MAVS-dependent interferon response. Our study reveals a mechanism for telomere-mediated tumour suppression, whereby dysfunctional telomeres activate innate immune responses through mitochondrial TERRA-ZBP1 complexes to eliminate cells destined for neoplastic transformation.

| S-EPMC9946831 | biostudies-literature

Telomere-to-mitochondria signaling by ZBP1 mediates replicative crisis (RIP-Seq)

Project description:Telomere-to-mitochondria signaling by ZBP1 mediates replicative crisis (RIP-Seq)

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Telomere-to-mitochondria signaling by ZBP1 mediates replicative crisis

Project description:Telomere-to-mitochondria signaling by ZBP1 mediates replicative crisis

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Telomere-to-mitochondria signaling by ZBP1 mediates replicative crisis

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-12-12 | GSE218396 | GEO

Telomere-to-mitochondria signaling by ZBP1 mediates replicative crisis (RNA-Seq)

Project description:Transcriptional response to telomere shortening or dysfunction

2022-12-12 | GSE218395 | GEO

Telomere-to-mitochondria signaling by ZBP1 mediates replicative crisis (RNA-Seq)

Project description:Telomere-to-mitochondria signaling by ZBP1 mediates replicative crisis (RNA-Seq)

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Expression data from ZBP1-expression and ZBP1 nonexpression breast tumors.

Project description:ZBP1/IMP1 is an mRNA binding protein that post-transcriptionally regulates the expression of a handful mRNAs, implicated in maintaining cell polarity and adhesion. We have previously shown that ZBP1 was able to inhibit proliferation and invasiveness of breast carcinoma cells in vitro. In the current study, we utilized orthotopic breast fat pad xenografts to further investigate the ZBP1-mediated functions in breast tumorigenesis and metastasis in vivo. We used microarrays to identify important gene for breast tumor growth and metastasis in response to ZBP1 expression Total RNA was extracted from breast tumor generated from ZBP1-expression and ZBP1-nonexpression MDA231 cells and used for hybridization on Affymetrix microarrays. We sought to obtain gene expression profiles from the individual tumors and identify what genes are up-regulated or down-regulated in the presence of ZBP1. The microarray experiments and data analysis were performed in 'Gene Company Limited' in Senzheng, China. G-10 and G-13, Tumors generated from MDA231/GFP cells; I-5 and I-6, tumors generated from MDA231/ZBP1-GFP cells.

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Expression data from ZBP1-expression and ZBP1 nonexpression breast tumors.

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Effcts of Zbp1 in B-cell lymphoma

Project description:B-cell lymphomas arising in Zbp1-/-Eu-Myc mice were compared to B-cell lymphomas arising in Zbp1+/+Eu-Myc mice

2014-04-01 | E-MTAB-2354 | biostudies-arrayexpress

Transcriptomic analysis of WT, Tfam+/-, Zbp1-/- and Tfam+/-Zbp1-/- mouse embryonic fibroblasts (MEFs)

Project description:The goal of this study was to compare the gene expression profiles of WT, Tfam+/-, Zbp1-/- and Tfam+/-Zbp1-/- MEFs.

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