ArticleThe Journal of biological chemistry2009
Amyotrophic lateral sclerosis-linked mutant SOD1 sequesters Hu antigen R (HuR) and TIA-1-related protein (TIAR): implications for impaired post-transcriptional regulation of vascular endothelial growth factor.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Meta-analysis of Genetic Modifiers Reveals Candidate Dysregulated Pathways in Amyotrophic Lateral Sclerosis.Neuroscience · 2019Pooled it
- The myokine FGF21 associates with enhanced survival in ALS and mitigates stress-induced cytotoxicity.Aging · 2025Article
- Fisetin Attenuates Mutant SOD1 Aggregation in Amyotrophic Lateral Sclerosis via Nrf2-Mediated Autophagy Activation.Journal of molecular neuroscience : MN · 2025Article
- Targets and Gene Therapy of ALS (Part 1).International journal of molecular sciences · 2025Review
- Nuclear pore dysfunction and disease: a complex opportunity.Nucleus (Austin, Tex.) · 2024Review
- The role of zinc in the premature brain: functions, outcomes and future research perspectives.Frontiers in pediatrics · 2024Review
- The long noncoding RNAScience advances · 2022Article
- T-Cell Intracellular Antigen 1-Like Protein in Physiology and Pathology.International journal of molecular sciences · 2022Review
- Alteration of Mitochondrial Integrity as Upstream Event in the Pathophysiology of SOD1-ALS.Cells · 2022Article
- Targeting the RNA-Binding Protein HuR as Potential Thera-Peutic Approach for Neurological Disorders: Focus on Amyo-Trophic Lateral Sclerosis (ALS), Spinal Muscle Atrophy (SMA) and Multiple Sclerosis.International journal of molecular sciences · 2021Review
- RNA Deregulation in Amyotrophic Lateral Sclerosis: The Noncoding Perspective.International journal of molecular sciences · 2021Review
- ALS-Linked Mutant SOD1 Associates with TIA-1 and Alters Stress Granule Dynamics.Neurochemical research · 2020Article
- Human antigen R-regulated mRNA metabolism promotes the cell motility of migrating mouse neurons.Development (Cambridge, England) · 2020Article
- Widespread FUS mislocalization is a molecular hallmark of amyotrophic lateral sclerosis.Brain : a journal of neurology · 2019Article
- Structural Properties and Interaction Partners of Familial ALS-Associated SOD1 Mutants.Frontiers in neurology · 2019Review
- Neuron-Specific HuR-Deficient Mice Spontaneously Develop Motor Neuron Disease.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- RNA Dysregulation in Amyotrophic Lateral Sclerosis.Frontiers in genetics · 2018Review
- T-Cell Intracellular Antigens and Hu Antigen R Antagonistically Modulate Mitochondrial Activity and Dynamics by Regulating Optic Atrophy 1 Gene Expression.Molecular and cellular biology · 2017Article
- An aberrant phase transition of stress granules triggered by misfolded protein and prevented by chaperone function.The EMBO journal · 2017Article
- RNA Binding Protein Regulation and Cross-Talk in the Control of AU-rich mRNA Fate.Frontiers in molecular biosciences · 2017Review
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Down-regulation of vascular endothelial growth factor (VEGF) in the mouse leads to progressive and selective degeneration of motor neurons similar to amyotrophic lateral sclerosis (ALS). In mice expressing ALS-associated mutant superoxide dismutase 1 (SOD1), VEGF mRNA expression in the spinal cord declines significantly prior to the onset of clinical manifestations. In vitro models suggest that dysregulation of VEGF mRNA stability contributes to that decline. Here, we show that the major RNA stabilizer, Hu Antigen R (HuR), and TIA-1-related protein (TIAR) colocalize with mutant SOD1 in mouse spinal cord extracts and cultured glioma cells. The colocalization was markedly reduced or abolished by RNase treatment. Immunoanalysis of transfected cells indicated that colocalization occurred in insoluble aggregates and inclusions. RNA immunoprecipitation showed a significant loss of VEGF mRNA binding to HuR and TIAR in mutant SOD1 cells, and there was marked depletion of HuR from polysomes. Ectopic expression of HuR in mutant SOD1 cells more than doubled the mRNA half-life of VEGF and significantly increased expression to that of wild-type SOD1 control. Cellular effects produced by mutant SOD1, including impaired mitochondrial function and oxidative stress-induced apoptosis, were reversed by HuR in a gene dose-dependent pattern. In summary, our findings indicate that mutant SOD1 impairs post-transcriptional regulation by sequestering key regulatory RNA-binding proteins. The rescue effect of HuR suggests that this impairment, whether related to VEGF or other potential mRNA targets, contributes to cytotoxicity in ALS.
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