ArticleMolecular medicine (Cambridge, Mass.)2014
Conditional knockout of the RNA-binding protein HuR in CD4⁺ T cells reveals a gene dosage effect on cytokine production.
Article in Molecular medicine (Cambridge, Mass.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- HuR Regulates GATA3-Driven Type 2 Inflammation in CD4bioRxiv : the preprint server for biology · 2026Article
- The glycolytic reaction PGAM restrains Th17 pathogenicity and Th17-dependent autoimmunity.Cell reports · 2025Article
- HuR ablation destabilizesFrontiers in immunology · 2025Article
- RNA-binding protein HuR reprograms immune T cells and promotes oral squamous cell carcinoma.Oral oncology reports · 2024Article
- NK cell expansion requires HuR and mediates control of solid tumors and long-term virus infection.The Journal of experimental medicine · 2023Article
- RNA Metabolism in T Lymphocytes.Immune network · 2022Review
- HuR as a molecular target for cancer therapeutics and immune-related disorders.Advanced drug delivery reviews · 2022Review
- Sequence determinants as key regulators in gene expression of T cells.Immunological reviews · 2021Review
- Post-transcriptional control of T-cell cytokine production: Implications for cancer therapy.Immunology · 2021Review
- HuR Plays a Positive Role to Strengthen the Signaling Pathways of CD4Journal of immunology research · 2021Article
- mRNA Post-Transcriptional Regulation by AU-Rich Element-Binding Proteins in Liver Inflammation and Cancer.International journal of molecular sciences · 2020Review
- RNA-Binding Protein HuR Promotes Th17 Cell Differentiation and Can Be Targeted to Reduce Autoimmune Neuroinflammation.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- HuR controls apoptosis and activation response without effects on cytokine 3' UTRs.RNA biology · 2019Article
- Posttranscriptional regulation of T helper cell fate decisions.The Journal of cell biology · 2018Review
- RNA-binding proteins control gene expression and cell fate in the immune system.Nature immunology · 2018Review
- Uncovering the Role of RNA-Binding Proteins in Gene Expression in the Immune System.Frontiers in immunology · 2018Review
- Regulation of HuR structure and function by dihydrotanshinone-I.Nucleic acids research · 2017Article
- The RNA-binding protein HuR contributes to neuroinflammation by promoting C-C chemokine receptor 6 (CCR6) expression on Th17 cells.The Journal of biological chemistry · 2017Article
- The RNA-Binding Protein HuR Posttranscriptionally Regulates IL-2 Homeostasis and CD4ImmunoHorizons · 2017Article
- CRISPR Knockout of the HuR Gene Causes a Xenograft Lethal Phenotype.Molecular cancer research : MCR · 2017Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
The posttranscriptional mechanisms by which RNA binding proteins (RBPs) regulate T-cell differentiation and cytokine production in vivo remain unclear. The RBP HuR binds to labile mRNAs, usually leading to increases in mRNA stability and/or translation. Previous work demonstrated that HuR binds to the mRNAs encoding the Th2 transcription factor trans-acting T-cell-specific transcription factor (GATA-3) and Th2 cytokines interleukin (IL)-4 and IL-13, thereby regulating their expression. By using a novel conditional HuR knockout (KO) mouse in which HuR is deleted in activated T cells, we show that Th2-polarized cells from heterozygous HuR conditional (OX40-Cre HuR(fl/+)) KO mice had decreased steady-state levels of Gata3, Il4 and Il13 mRNAs with little changes at the protein level. Surprisingly, Th2-polarized cells from homozygous HuR conditional (OX40-Cre HuR(fl/fl)) KO mice showed increased Il2, Il4 and Il13 mRNA and protein via different mechanisms. Specifically, Il4 was transcriptionally upregulated in HuR KO T cells, whereas Il2 and Il13 mRNA stabilities increased. Additionally, when using the standard ovalbumin model of allergic airway inflammation, HuR conditional KO mice mounted a robust inflammatory response similar to mice with wild-type HuR levels. These results reveal a complex differential posttranscriptional regulation of cytokines by HuR in which gene dosage plays an important role. These findings may have significant implications in allergies and asthma, as well as autoimmune diseases and infection.
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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.