ArticleArteriosclerosis, thrombosis, and vascular biology2014
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.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
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- Obesity: pathophysiology and therapeutic interventions.Molecular biomedicine · 2025Review
- Pathogenic LDLR Variants (c.103 C>T and c.2416dup) in ligand-binding and cytosolic domains in Saudi familial hypercholesterolemia: Molecular characterization and computational insights.Computational and structural biotechnology journal · 2025Article
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- Posttranscriptional regulation of the T-box gene midline via the 3'UTR in Drosophila is complex and cell- and tissue-dependent.Genetics · 2024Article
- Gut ribotoxic stress responses facilitate dyslipidemia via metabolic reprogramming: an environmental health prediction.Theranostics · 2024Article
- Efficacy and underlying mechanisms of berberine against lipid metabolic diseases: a review.Frontiers in pharmacology · 2023Review
- Oral Delivery of Nucleic Acid Therapies for Local and Systemic Action.Pharmaceutical research · 2023Review
- Cold shock domain-containing protein E1 is a posttranscriptional regulator of the LDL receptor.Science translational medicine · 2022Article
- Drug delivery approaches for HuR-targeted therapy for lung cancer.Advanced drug delivery reviews · 2022Review
- Regulation of low-density lipoprotein receptor expression in triple negative breast cancer by EGFR-MAPK signaling.Scientific reports · 2021Article
- Biological properties and clinical applications of berberine.Frontiers of medicine · 2020Review
- Promising Anti-atherosclerotic Effect of Berberine: Evidence from In Vitro, In Vivo, and Clinical Studies.Reviews of physiology, biochemistry and pharmacology · 2020Review
- Berberine decreases plasma triglyceride levels and upregulates hepatic TRIB1 in LDLR wild type mice and in LDLR deficient mice.Scientific reports · 2019Article
- Farnesoid X Receptor Activation by Obeticholic Acid Elevates Liver Low-Density Lipoprotein Receptor Expression by mRNA Stabilization and Reduces Plasma Low-Density Lipoprotein Cholesterol in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
- Berberine is a potential therapeutic agent for metabolic syndrome via brown adipose tissue activation and metabolism regulation.American journal of translational research · 2018Review
- Effect of Leptin Replacement on PCSK9 in ob/ob Mice and Female Lipodystrophic Patients.Endocrinology · 2016Article
- Article
- Cholesterol and lipoprotein metabolism: Early Career Committee contribution.Arteriosclerosis, thrombosis, and vascular biology · 2014Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
objectivePrevious 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
resultsWe 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.
conclusionshnRNP 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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.