The RNA-binding protein vigilin regulates VLDL secretion through modulation of Apob mRNA translation

Mobin, M. B. and Gerstberger, S. and Teupser, D. and Campana, B. and Charisse, K. and Heim, M. H. and Manoharan, M. and Tuschl, T. and Stoffel, M.. (2016) The RNA-binding protein vigilin regulates VLDL secretion through modulation of Apob mRNA translation. Nat Commun, 7. p. 12848.

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Official URL: https://edoc.unibas.ch/61797/

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The liver is essential for the synthesis of plasma proteins and integration of lipid metabolism. While the role of transcriptional networks in these processes is increasingly understood, less is known about post-transcriptional control of gene expression by RNA-binding proteins (RBPs). Here, we show that the RBP vigilin is upregulated in livers of obese mice and in patients with fatty liver disease. By using in vivo, biochemical and genomic approaches, we demonstrate that vigilin controls very-low-density lipoprotein (VLDL) secretion through the modulation of apolipoproteinB/Apob mRNA translation. Crosslinking studies reveal that vigilin binds to CU-rich regions in the mRNA coding sequence of Apob and other proatherogenic secreted proteins, including apolipoproteinC-III/Apoc3 and fibronectin/Fn1. Consequently, hepatic vigilin knockdown decreases VLDL/low-density lipoprotein (LDL) levels and formation of atherosclerotic plaques in Ldlr-/- mice. These studies uncover a role for vigilin as a key regulator of hepatic Apob translation and demonstrate the therapeutic potential of inhibiting vigilin for cardiovascular diseases.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Hepatology Laboratory (Heim)
UniBasel Contributors:Heim, Markus H.
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:2041-1723 (Electronic) 2041-1723 (Linking)
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:31 May 2020 21:29
Deposited On:31 May 2020 21:29

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