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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<jats:italic>in vivo<\/jats:italic>, biochemical and genomic approaches, we demonstrate that vigilin controls very-low-density lipoprotein (VLDL) secretion through the modulation of apolipoproteinB\/<jats:italic>Apob<\/jats:italic>mRNA translation. Crosslinking studies reveal that vigilin binds to CU-rich regions in the mRNA coding sequence of<jats:italic>Apob<\/jats:italic>and other proatherogenic secreted proteins, including apolipoproteinC-III\/<jats:italic>Apoc3<\/jats:italic>and fibronectin\/<jats:italic>Fn1<\/jats:italic>. Consequently, hepatic vigilin knockdown decreases VLDL\/low-density lipoprotein (LDL) levels and formation of atherosclerotic plaques in<jats:italic>Ldlr<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>mice. These studies uncover a role for vigilin as a key regulator of hepatic<jats:italic>Apob<\/jats:italic>translation and demonstrate the therapeutic potential of inhibiting vigilin for cardiovascular diseases.<\/jats:p>","DOI":"10.1038\/ncomms12848","type":"journal-article","created":{"date-parts":[[2016,9,26]],"date-time":"2016-09-26T12:14:54Z","timestamp":1474892094000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["The RNA-binding protein vigilin regulates VLDL secretion through modulation of Apob mRNA translation"],"prefix":"10.1038","volume":"7","author":[{"given":"Mehrpouya B.","family":"Mobin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Gerstberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Teupser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedetta","family":"Campana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Charisse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus H.","family":"Heim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muthiah","family":"Manoharan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Tuschl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Stoffel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,9,26]]},"reference":[{"key":"BFncomms12848_CR1","doi-asserted-by":"crossref","first-page":"12131","DOI":"10.1016\/S0021-9258(19)49815-3","volume":"267","author":"GL McKnight","year":"1992","unstructured":"McKnight, G. 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