ArticleMolecular and cellular biology2004
Distinct domains of AU-rich elements exert different functions in mRNA destabilization and stabilization by p38 mitogen-activated protein kinase or HuR.
Article in Molecular and cellular biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 125 citations in OpenAlex.
- Posttranscriptional control of hepatic CEACAM1 3'UTR by human antigen R (HuR) mitigates sterile liver inflammation.JCI insight · 2025Article
- Targeting the RNA-Binding Protein HuR in Cancer.Cancer research · 2023Review
- Understanding and targeting the disease-related RNA binding protein human antigen R (HuR).Wiley interdisciplinary reviews. RNA · 2020Review
- Novel AU-rich proximal UTR sequences (APS) enhance CXCL8 synthesis upon the induction of rpS6 phosphorylation.PLoS genetics · 2019Article
- Membrane-associated RING-CH (MARCH) 1 and 2 are MARCH family members that inhibit HIV-1 infection.The Journal of biological chemistry · 2019Article
- Post-transcriptional regulation of cytokine expression and signaling.Current trends in immunology · 2018Article
- An Epstein-Barr Virus MicroRNA Blocks Interleukin-1 (IL-1) Signaling by Targeting IL-1 Receptor 1.Journal of virology · 2017Article
- Human antigen R-regulated CCL20 contributes to osteolytic breast cancer bone metastasis.Scientific reports · 2017Article
- The control of inflammation via the phosphorylation and dephosphorylation of tristetraprolin: a tale of two phosphatases.Biochemical Society transactions · 2016Review
- Sustained stabilization of Interleukin-8 mRNA in human macrophages.RNA biology · 2014Article
- Cigarette smoke enhances human rhinovirus-induced CXCL8 production via HuR-mediated mRNA stabilization in human airway epithelial cells.Respiratory research · 2013Article
- Luteolin inhibits inflammatory responses via p38/MK2/TTP-mediated mRNA stability.Molecules (Basel, Switzerland) · 2013Article
- Diversity in sequence-dependent control of GRO chemokine mRNA half-life.Journal of leukocyte biology · 2013Article
- Impairment of FOS mRNA stabilization following translation arrest in granulocytes from myelodysplastic syndrome patients.PloS one · 2013Article
- Cell type- and stimulus-specific mechanisms for post-transcriptional control of neutrophil chemokine gene expression.Journal of leukocyte biology · 2012Review
- 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
- Characterization of 3'-untranslated region of the mouse GDNF gene.BMC molecular biology · 2012Article
- HuR function in disease.Frontiers in bioscience (Landmark edition) · 2012Review
- Parthenolide inhibits ERK and AP-1 which are dysregulated and contribute to excessive IL-8 expression and secretion in cystic fibrosis cells.Journal of inflammation (London, England) · 2011Article
- Interleukin-1 activates synthesis of interleukin-6 by interfering with a KH-type splicing regulatory protein (KSRP)-dependent translational silencing mechanism.The Journal of biological chemistry · 2011Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
AU-rich elements (AREs) control the expression of numerous genes by accelerating the decay of their mRNAs. Rapid decay and deadenylation of beta-globin mRNA containing AU-rich 3' untranslated regions of the chemoattractant cytokine interleukin-8 (IL-8) are strongly attenuated by activating the p38 mitogen-activated protein (MAP) kinase/MAP kinase-activated protein kinase 2 (MK2) pathway. Further evidence for a crucial role of the poly(A) tail is provided by the loss of destabilization and kinase-induced stabilization in ARE RNAs expressed as nonadenylated forms by introducing a histone stem-loop sequence. The minimal regulatory element in the IL-8 mRNA is located in a 60-nucleotide evolutionarily conserved sequence with a structurally and functionally bipartite character: a core domain with four AUUUA motifs and limited destabilizing function on its own and an auxiliary domain that markedly enhances destabilization exerted by the core domain and thus is essential for the rapid removal of RNA targets. A similar bipartite structure and function are observed for the granulocyte-macrophage colony-stimulating factor (GM-CSF) ARE. Stabilization in response to p38/MK2 activation is seen with the core domain alone and also after mutation of the AUUUA motifs in the complete IL-8 ARE. Stabilization by ARE binding protein HuR requires different sequence elements. Binding but no stabilization is observed with the IL-8 ARE. Responsiveness to HuR is gained by exchanging the auxiliary domain of the IL-8 ARE with that of GM-CSF or with a domain of the c-fos ARE, which results in even stronger responsiveness. These results show that distinct ARE domains differ in function with regard to destabilization, stabilization by p38/MK2 activation, and stabilization by HuR.
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