Tags

Type your tag names separated by a space and hit enter

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 Feb 11; 21(4)IJ

Abstract

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.

Links

PMC Free PDF

Authors+Show Affiliations

Siculella L
Laboratory of Molecular Biology, Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy.
Giannotti L
Laboratory of Molecular Biology, Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy.
Testini M
Laboratory of Molecular Biology, Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy.
Gnoni GV
Laboratory of Biochemistry, Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy.
Damiano F
Laboratory of Molecular Biology, Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy.

MeSH

5' Untranslated RegionsATP Citrate (pro-S)-LyaseEndoplasmic Reticulum StressHep G2 CellsHepatocytesHumansLipogenesisNon-alcoholic Fatty Liver DiseaseProtein BiosynthesisRNA, Messenger

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32054087

Citation

Siculella, Luisa, et al. "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, vol. 21, no. 4, 2020.
Siculella L, Giannotti L, Testini M, et al. 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(4).
Siculella, L., Giannotti, L., Testini, M., Gnoni, G. V., & Damiano, F. (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(4). https://doi.org/10.3390/ijms21041206
Siculella L, et al. 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 Feb 11;21(4) PubMed PMID: 32054087.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In Steatotic Cells, ATP-Citrate Lyase mRNA Is Efficiently Translated through a Cap-Independent Mechanism, Contributing to the Stimulation of De Novo Lipogenesis. AU - Siculella,Luisa, AU - Giannotti,Laura, AU - Testini,Mariangela, AU - Gnoni,Gabriele V, AU - Damiano,Fabrizio, Y1 - 2020/02/11/ PY - 2020/01/18/received PY - 2020/02/04/revised PY - 2020/02/05/accepted PY - 2020/2/15/entrez PY - 2020/2/15/pubmed PY - 2020/11/21/medline KW - ATP-citrate lyase KW - Cap-independent translation KW - de novo lipogenesis KW - endoplasmic reticulum stress KW - internal ribosome entry site KW - lipid droplets KW - non-alcoholic fatty liver diseases JF - International journal of molecular sciences JO - Int J Mol Sci VL - 21 IS - 4 N2 - 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. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/32054087/In_Steatotic_Cells_ATP_Citrate_Lyase_mRNA_Is_Efficiently_Translated_through_a_Cap_Independent_Mechanism_Contributing_to_the_Stimulation_of_De_Novo_Lipogenesis_ DB - PRIME DP - Unbound Medicine ER -