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Article

In Steatotic Cells, ATP-Citrate Lyase mRNA Is Efficiently Translated through a Cap-Independent Mechanism, Contributing to the Stimulation of De Novo Lipogenesis

1
Laboratory of Molecular Biology, Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy
2
Laboratory of Biochemistry, Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(4), 1206; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21041206
Received: 18 January 2020 / Revised: 4 February 2020 / Accepted: 5 February 2020 / Published: 11 February 2020
(This article belongs to the Special Issue Translational Control 2.0)
Non-alcoholic fatty liver disease (NAFLD) is a chronic disease in which excessive amount of lipids is accumulated as droplets in hepatocytes. Recently, cumulative evidences suggested that a sustained de novo lipogenesis can play an important role in NAFLD. Dysregulated expression of lipogenic genes, including ATP-citrate lyase (ACLY), has been found in liver diseases associated with lipid accumulation. ACLY is a ubiquitous cytosolic enzyme positioned at the intersection of nutrients catabolism and cholesterol and fatty acid biosyntheses. In the present study, the molecular mechanism of ACLY expression in a cell model of steatosis has been reported. We identified an internal ribosome entry site (IRES) in the 5′ untranslated region of the ACLY mRNA, that can support an efficient mRNA translation through a Cap-independent mechanism. In steatotic HepG2 cells, ACLY expression was up-regulated through IRES-mediated translation. Since it has been demonstrated that lipid accumulation in cells induces endoplasmic reticulum (ER) stress, the involvement of this cellular pathway in the translational regulation of ACLY has been also evaluated. Our results showed that ACLY expression was increased in ER-stressed cells, through IRES-mediated translation of ACLY mRNA. A potential role of the Cap-independent translation of ACLY in NAFLD has been discussed. View Full-Text
Keywords: ATP-citrate lyase; Cap-independent translation; de novo lipogenesis; endoplasmic reticulum stress; internal ribosome entry site; lipid droplets; non-alcoholic fatty liver diseases ATP-citrate lyase; Cap-independent translation; de novo lipogenesis; endoplasmic reticulum stress; internal ribosome entry site; lipid droplets; non-alcoholic fatty liver diseases
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MDPI and ACS Style

Siculella, L.; Giannotti, L.; Testini, M.; Gnoni, G.V.; Damiano, F. In Steatotic Cells, ATP-Citrate Lyase mRNA Is Efficiently Translated through a Cap-Independent Mechanism, Contributing to the Stimulation of De Novo Lipogenesis. Int. J. Mol. Sci. 2020, 21, 1206. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21041206

AMA Style

Siculella L, Giannotti L, Testini M, Gnoni GV, Damiano F. In Steatotic Cells, ATP-Citrate Lyase mRNA Is Efficiently Translated through a Cap-Independent Mechanism, Contributing to the Stimulation of De Novo Lipogenesis. International Journal of Molecular Sciences. 2020; 21(4):1206. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21041206

Chicago/Turabian Style

Siculella, Luisa, Laura Giannotti, Mariangela Testini, Gabriele V. Gnoni, and Fabrizio Damiano. 2020. "In Steatotic Cells, ATP-Citrate Lyase mRNA Is Efficiently Translated through a Cap-Independent Mechanism, Contributing to the Stimulation of De Novo Lipogenesis" International Journal of Molecular Sciences 21, no. 4: 1206. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21041206

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