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http://purl.uniprot.org/citations/24158514http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24158514http://www.w3.org/2000/01/rdf-schema#comment"

Objective

Previous studies showed that low-density lipoprotein receptor (LDLR) mRNA 3' untranslated region (UTR) contains regulatory elements responsible for rapid mRNA turnover in hepatic cells and mediates the mRNA stabilization induced by berberine (BBR). Here, we elucidate the underlying mechanism of BBR's action by characterizing mRNA-binding proteins that modulate LDLR mRNA decay via 3'UTR in liver tissue in vivo.

Approach and results

We generated a transgenic mouse model (Alb-Luc-UTR) that expresses Luc-LDLR3'UTR reporter gene driven by the albumin promoter to study 3'UTR function in mediating LDLR mRNA decay in liver tissue. We show that treating Alb-Luc-UTR mice with BBR led to significant increases in hepatic bioluminescence signals, Luc-UTR mRNA, and LDLR mRNA levels as compared with control mice. These effects were accompanied by specific reductions of mRNA decay-promoting factor heterogeneous nuclear ribonucleoprotein D (hnRNP D) in liver of BBR-treated mice. Knockdown and overexpression studies further demonstrated that hnRNP D p37 isoform plays a major role in promoting hepatic LDLR mRNA degradation. In addition, we examined LDLR mRNA half-life, Luc-UTR reporter activity, and hnRNP D expression levels in cell lines derived from extrahepatic tissues. We demonstrated that strengths of 3'UTR in promoting mRNA degradation correlate with hnRNP D cellular abundances in nonhepatic cell lines, thereby suggesting its involvement in LDLR mRNA degradation beyond liver tissue.

Conclusions

hnRNP D is critically involved in LDLR mRNA degradation in liver tissue in vivo. The inverse relationship of hnRNP D abundance with LDLR mRNA levels after BBR treatment suggests the potential of hnRNP D of being a novel therapeutic target for LDL cholesterol lowering."xsd:string
http://purl.uniprot.org/citations/24158514http://purl.org/dc/terms/identifier"doi:10.1161/atvbaha.112.301131"xsd:string
http://purl.uniprot.org/citations/24158514http://purl.uniprot.org/core/author"Li H."xsd:string
http://purl.uniprot.org/citations/24158514http://purl.uniprot.org/core/author"Liu J."xsd:string
http://purl.uniprot.org/citations/24158514http://purl.uniprot.org/core/author"Dong B."xsd:string
http://purl.uniprot.org/citations/24158514http://purl.uniprot.org/core/author"Singh A.B."xsd:string
http://purl.uniprot.org/citations/24158514http://purl.uniprot.org/core/author"Nicolls M.R."xsd:string
http://purl.uniprot.org/citations/24158514http://purl.uniprot.org/core/author"Kan C.F."xsd:string
http://purl.uniprot.org/citations/24158514http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/24158514http://purl.uniprot.org/core/name"Arterioscler Thromb Vasc Biol"xsd:string
http://purl.uniprot.org/citations/24158514http://purl.uniprot.org/core/pages"8-16"xsd:string
http://purl.uniprot.org/citations/24158514http://purl.uniprot.org/core/title"The critical role of mRNA destabilizing protein heterogeneous nuclear ribonucleoprotein d in 3' untranslated region-mediated decay of low-density lipoprotein receptor mRNA in liver tissue."xsd:string
http://purl.uniprot.org/citations/24158514http://purl.uniprot.org/core/volume"34"xsd:string
http://purl.uniprot.org/citations/24158514http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/24158514
http://purl.uniprot.org/citations/24158514http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/24158514
http://purl.uniprot.org/uniprot/#_A0A1L1SRE8-mappedCitation-24158514http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24158514
http://purl.uniprot.org/uniprot/#_A0A0G2JFL4-mappedCitation-24158514http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24158514
http://purl.uniprot.org/uniprot/#_B4DTC3-mappedCitation-24158514http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24158514
http://purl.uniprot.org/uniprot/#_B4E0W4-mappedCitation-24158514http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24158514
http://purl.uniprot.org/uniprot/#_E9Q4W5-mappedCitation-24158514http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24158514
http://purl.uniprot.org/uniprot/#_E9Q5B6-mappedCitation-24158514http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24158514
http://purl.uniprot.org/uniprot/#_F6SHF3-mappedCitation-24158514http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24158514
http://purl.uniprot.org/uniprot/#_G5E8G0-mappedCitation-24158514http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24158514
http://purl.uniprot.org/uniprot/#_F6ZV59-mappedCitation-24158514http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24158514
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