ArticleNucleic acids research2001
Polymorphism in the 3'-untranslated region of TNFalpha mRNA impairs binding of the post-transcriptional regulatory protein HuR to TNFalpha mRNA.
Article in Nucleic acids research, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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34 citing papers in PubMed, 82 citations in OpenAlex.
- Article
- RNA-binding proteins and RNA methylation in myeloid cells.Immunological reviews · 2021Review
- Genetic variant of cyclooxygenase-2 in gastric cancer: More inflammation and susceptibility.World journal of gastroenterology · 2021Review
- Association of the cyclooxygenase-2 1759A allele with migraine in Chinese Han individuals.PloS one · 2020Article
- HuR counteracts miR-330 to promote STAT3 translation during inflammation-induced muscle wasting.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Genetic variants in mRNA untranslated regions.Wiley interdisciplinary reviews. RNA · 2018Review
- Toll-like receptor 4 rs11536889 is associated with angiographic extent and severity of coronary artery disease in a Chinese population.Oncotarget · 2017Article
- Association of inflammatory gene polymorphisms with mechanical heart valve reoperation.SpringerPlus · 2016Article
- Association of the C-Reactive Protein Gene (CRP) rs1205 C>T Polymorphism with Aortic Valve Calcification in Patients with Aortic Stenosis.International journal of molecular sciences · 2015Article
- Translating the Untranslated Region.Journal of immunology (Baltimore, Md. : 1950) · 2015Review
- Polymorphisms in cyclooxygenase-2 gene in endometrial cancer patients.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Inactivation of the mTORC1-eukaryotic translation initiation factor 4E pathway alters stress granule formation.Molecular and cellular biology · 2013Article
- Involvement of fibroblast growth factor receptor genes in benign prostate hyperplasia in a Korean population.Disease markers · 2013Article
- Article
- The p38/MK2-driven exchange between tristetraprolin and HuR regulates AU-rich element-dependent translation.PLoS genetics · 2012Article
- The complex world of post-transcriptional mechanisms: is their deregulation a common link for diseases? Focus on ELAV-like RNA-binding proteins.Cellular and molecular life sciences : CMLS · 2012Review
- A long AAAG repeat allele in the 5' UTR of the ERR-γ gene is correlated with breast cancer predisposition and drives promoter activity in MCF-7 breast cancer cells.Breast cancer research and treatment · 2011Article
- Transportin 2 regulates apoptosis through the RNA-binding protein HuR.The Journal of biological chemistry · 2011Article
- Sporadic breast cancer patients' germline DNA exhibit an AT-rich microsatellite signature.Genes, chromosomes & cancer · 2011Article
- Identification of a shared F8 mutation in the Korean patients with acquired hemophilia A.The Korean journal of hematology · 2011Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor necrosis factor alpha (TNFalpha) acts as a beneficial mediator in the process of host defence. In recent years major interest has focused on the AU-rich elements (AREs) present in the 3'-untranslated region (3'-UTR) of TNFalpha mRNA as this region plays a pivotal role in post-transcriptional control of TNFalpha production. Certain stimuli, such as lipopolysaccharides, a component of the Gram-negative bacterial cell wall, have the ability to relinquish the translational suppression of TNFalpha mRNA imposed by these AREs in macrophages, thereby enabling the efficient production of the TNFalpha. In this study we show that the polymorphism (GAU trinucleotide insertional mutation) present in the regulatory 3'-UTR of TNFalpha mRNA of NZW mice results in the hindered binding of RNA-binding proteins, thereby leading to a significantly reduced production of TNFalpha protein. We also show that the binding of macrophage proteins to the main ARE is also decreased by another trinucleotide (CAU) insertion in the TNFalpha 3'-UTR. One of the proteins affected by the GAU trinucleotide insertional mutation was identified as HuR, a nucleo-cytoplasmic shuttling protein previously shown to play a prominent role in the stability and translatability of mRNA containing AREs. Since binding of this protein most likely modulates the stability, translational efficiency and transport of TNFalpha mRNA, these results suggest that mutations in the ARE of TNFalpha mRNA decrease the production of TNFalpha protein in macrophages by hindering the binding of HuR to the ARE.
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