Cytolethal distending toxin induces the formation of transient messenger-rich ribonucleoprotein nuclear invaginations in surviving cells

Autoři: Lamia Azzi-Martin aff001;  Wencan He aff001;  Christelle Péré-Védrenne aff001;  Victoria Korolik aff002;  Chloé Alix aff001;  Martina Prochazkova-Carlotti aff001;  Jean-Luc Morel aff003;  Emilie Le Roux-Goglin aff001;  Philippe Lehours aff001;  Mojgan Djavaheri-Mergny aff005;  Christophe F. Grosset aff006;  Christine Varon aff001;  Pierre Dubus aff001;  Armelle Ménard aff001
Působiště autorů: Univ. Bordeaux, INSERM, Bordeaux Research in Translational Oncology, BaRITOn, U1053, Bordeaux, France aff001;  Institute for Glycomics, Griffith University, Gold Coast Campus, Gold Coast, Australia aff002;  Univ. Bordeaux, CNRS; UMR5293, Institut des maladies neurodégénératives, Bordeaux, France aff003;  CHU de Bordeaux, Laboratoire de Bactériologie, Centre National de Référence des Campylobacters et des Hélicobacters, Bordeaux, France aff004;  Univ. Bordeaux, INSERM U1218 ACTION, Institut Bergonié, Bordeaux France, INSERM U1138, Centre de Recherche des Cordeliers, Paris, France. Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, Villejuif, France aff005;  Univ. Bordeaux, INSERM, Biothérapies des Maladies Génétiques, Inflammatoires et Cancer, BMGIC, U1035, Bordeaux, France aff006;  CHU de Bordeaux, Pôle biologie et pathologie, Service de biologie des tumeurs, Bordeaux, France aff007
Vyšlo v časopise: Cytolethal distending toxin induces the formation of transient messenger-rich ribonucleoprotein nuclear invaginations in surviving cells. PLoS Pathog 15(9): e32767. doi:10.1371/journal.ppat.1007921
Kategorie: Research Article
doi: 10.1371/journal.ppat.1007921


Humans are frequently exposed to bacterial genotoxins involved in digestive cancers, colibactin and Cytolethal Distending Toxin (CDT), the latter being secreted by many pathogenic bacteria. Our aim was to evaluate the effects induced by these genotoxins on nuclear remodeling in the context of cell survival. Helicobacter infected mice, coculture experiments with CDT- and colibactin-secreting bacteria and hepatic, intestinal and gastric cells, and xenograft mouse-derived models were used to assess the nuclear remodeling in vitro and in vivo. Our results showed that CDT and colibactin induced-nuclear remodeling can be associated with the formation of deep cytoplasmic invaginations in the nucleus of giant cells. These structures, observed both in vivo and in vitro, correspond to nucleoplasmic reticulum (NR). The core of the NR was found to concentrate ribosomes, proteins involved in mRNA translation, polyadenylated RNA and the main components of the complex mCRD involved in mRNA turnover. These structures are active sites of mRNA translation, correlated with a high degree of ploidy, and involve MAPK and calcium signaling. Additional data show that insulation and concentration of these adaptive ribonucleoprotein particles within the nucleus are dynamic, transient and protect the cell until the genotoxic stress is relieved. Bacterial genotoxins-induced NR would be a privileged gateway for selected mRNA to be preferably transported therein for local translation. These findings offer new insights into the context of NR formation, a common feature of many cancers, which not only appears in response to therapies-induced DNA damage but also earlier in response to genotoxic bacteria.

Klíčová slova:

Cell staining – Cytoplasm – Cytoplasmic staining – DAPI staining – DNA damage – Fluorescence imaging – Messenger RNA – Nuclear staining


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