ArticlePloS one2011
Coordinately regulated alternative splicing of genes involved in cholesterol biosynthesis and uptake.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 67 citations in OpenAlex.
- ZNF542P is a pseudogene associated with LDL response to simvastatin treatment.Scientific reports · 2018Trial
- Exercise ModulatesInternational journal of molecular sciences · 2026Article
- Impact of mRNA and protein isoforms in lipoprotein metabolism and how to modulate them.Current opinion in lipidology · 2026Review
- Splice Isoforms of the Apoptosis Gene BCL-X Have Opposing Effects in Diabetic Kidney Disease: Potential Treatment Target and Prognostic Value.Journal of diabetes research · 2026Article
- Alternative Splicing Regulation in Metabolic Disorders.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Review
- PTBP1 and Cancer: From RNA Regulation to Therapeutic Potential.Journal of cellular and molecular medicine · 2025Review
- Epigenetic Modifications in Alternative Splicing of LDLR pre-mRNA on Hypercholesterolemia Following Aerobic Exercise Training.International journal of molecular sciences · 2025Article
- The Effect of Plastic-Related Compounds on Transcriptome-Wide Gene Expression on CYP2C19-Overexpressing HepG2 Cells.Molecules (Basel, Switzerland) · 2023Article
- Review
- Vitamin E Derivative with Modified Side Chain Induced Apoptosis by Modulating the Cellular Lipids and Membrane Dynamics in MCF7 Cells.Cell biochemistry and biophysics · 2021Article
- Elucidation of the BMI1 interactome identifies novel regulatory roles in glioblastoma.NAR cancer · 2021Article
- Multi-Dimensional Transcriptome Analysis Reveals Modulation of Cholesterol Metabolism as Highly Integrated Response to Brain Injury.Frontiers in neuroscience · 2021Article
- Article
- Targeting SREBP-2-Regulated Mevalonate Metabolism for Cancer Therapy.Frontiers in oncology · 2020Review
- Proteolytic Control of Lipid Metabolism.ACS chemical biology · 2019Review
- Influence of 6 genetic variants on the efficacy of statins in patients with dyslipidemia.Journal of clinical laboratory analysis · 2018Article
- Functionally specific binding regions of microtubule-associated protein 2c exhibit distinct conformations and dynamics.The Journal of biological chemistry · 2018Article
- Rapid and Dynamic Alternative Splicing Impacts the Arabidopsis Cold Response Transcriptome.The Plant cell · 2018Article
- The emerging role of alternative splicing in senescence and aging.Aging cell · 2017Review
- Statin-induced expression change of INSIG1 in lymphoblastoid cell lines correlates with plasma triglyceride statin response in a sex-specific manner.The pharmacogenomics journal · 2017Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Genes involved in cholesterol biosynthesis and uptake are transcriptionally regulated in response to cellular sterol content in a coordinated manner. A number of these genes, including 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) and LDL receptor (LDLR), undergo alternative splicing, resulting in reductions of enzyme or protein activity. Here we demonstrate that cellular sterol depletion suppresses, and sterol loading induces, alternative splicing of multiple genes involved in the maintenance of cholesterol homeostasis including HMGCR and LDLR, the key regulators of cellular cholesterol biosynthesis and uptake, respectively. These changes were observed in both in vitro studies of the HepG2 human hepatoma derived cell line, as well as in vivo studies of St. Kitts vervets, also known as African green monkeys, a commonly used primate model for investigating cholesterol metabolism. These effects are mediated in part by sterol regulation of polypyrimidine tract binding protein 1 (PTBP1), since knock-down of PTBP1 eliminates sterol induced changes in alternative splicing of several of these genes. Single nucleotide polymorphisms (SNPs) that influence HMGCR and LDLR alternative splicing (rs3846662 and rs688, respectively), have been associated with variation in plasma LDL-cholesterol levels. Sterol-induced changes in alternative splicing are blunted in carriers of the minor alleles for each of these SNPs, indicating an interaction between genetic and non-genetic regulation of this process. Our results implicate alternative splicing as a novel mechanism of enhancing the robust transcriptional response to conditions of cellular cholesterol depletion or accumulation. Thus coordinated regulation of alternative splicing may contribute to cellular cholesterol homeostasis as well as plasma LDL levels.
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Registered trials
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.