Accelerated export of Dicer1 from lipid-challenged hepatocytes buffers cellular miRNA-122 levels and prevents cell death
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Le résumé fourni par la source
Hepatocytes on exposure to high levels of lipids reorganize the metabolic program while fighting against the toxicity associated with elevated cellular lipids. The mechanism of this metabolic reorientation and stress management in lipid-challenged hepatocytes has not been well explored. We have noted the lowering of miR-122, a liver-specific miRNA, in the liver of mice fed with either a high-fat diet or a methionine-choline-deficient diet that is associated with increased fat accumulation in mice liver. Interestingly, low miR-122 levels are attributed to the enhanced extracellular export of miRNA processor enzyme Dicer1 from hepatocytes in the presence of high lipids. Export of Dicer1 can also account for the increased cellular levels of pre-miR-122-the substrate of Dicer1. Interestingly, restoration of Dicer1 levels in the mouse liver resulted in a strong inflammatory response and cell death in the presence of high lipids. Increasing death of hepatocytes was found to be caused by increased miR-122 levels in hepatocytes restored for Dicer1. Thus, the Dicer1 export by hepatocytes seems to be a key mechanism to combat lipotoxic stress by shunting out miR-122 from stressed hepatocytes. Finally, as part of this stress management, we determined that the Ago2-interacting pool of Dicer1, responsible for mature microribonucleoprotein formation in mammalian cells, gets depleted. miRNA-binder and exporter protein HuR is found to accelerate Ago2-Dicer1 uncoupling to ensure export of Dicer1 via extracellular vesicles in lipid-loaded hepatocytes.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Accelerated export of Dicer1 from lipid-challenged hepatocytes buffers cellular miRNA-122 levels and prevents cell death
- Date Crossref
- 01/08/2023
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Indian Institute of Chemical Biology Structural Biology and Bio-Informatics Division pays non établi dans la noticeStructure de recherche
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Netaji Subhas Chandra Bose Cancer Research Institute Department of Molecular Biology pays non établi dans la noticeÉtablissement de santé
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Nebraska Medical Center RNA Biology Research Laboratory pays non établi dans la noticeÉtablissement de santé
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University of Nebraska Medical Center pays non établi dans la noticeÉtablissement de santé
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RNA Biology Research Laboratory pays non établi dans la noticeStructure de recherche
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Metabolic Disease Laboratory pays non établi dans la noticeStructure de recherche
Structural Biology and Bio-Informatics Division — Indian Institute of Chemical Biology, Department of Molecular Biology — Netaji Subhas Chandra Bose Cancer Research Institute et RNA Biology Research Laboratory — Nebraska Medical Center, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.