ArticleHuman molecular genetics2015
Deleterious mutations in the essential mRNA metabolism factor, hGle1, in amyotrophic lateral sclerosis.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 128 citations in OpenAlex.
- Temporal gating dictates stress-induced transcript export from the nucleus.Genes & development · 2026Article
- Maintenance and disruption of the physiological dimer structure of TDP-43 in amyotrophic lateral sclerosis and frontotemporal lobar degeneration.BMC medicine · 2026Review
- Pathologies at the gateway: exploring the link between nucleoporins and inherited diseases.Cellular and molecular life sciences : CMLS · 2026Review
- Temporal gating dictates stress-induced transcript export from the nucleus.bioRxiv : the preprint server for biology · 2026Article
- A heterozygous 9q34 deletion encompassing SPTAN1 as a cause of distal myopathy.European journal of human genetics : EJHG · 2026Article
- In vivo modeling of lethal congenital contracture syndrome 1 suggests pathomechanisms in cellular stress responses.The FEBS journal · 2025Article
- Entering the era of precision medicine to treat amyotrophic lateral sclerosis.Molecular neurodegeneration · 2025Review
- The nuclear envelope and nuclear pore complexes in neurodegenerative diseases.Frontiers in cell and developmental biology · 2025Review
- Nuclear pore dysfunction and disease: a complex opportunity.Nucleus (Austin, Tex.) · 2024Review
- Heterogeneous Nuclear Ribonucleoprotein A1 Knockdown Alters Constituents of Nucleocytoplasmic Transport.Brain sciences · 2024Article
- Advances in the understanding of nuclear pore complexes in human diseases.Journal of cancer research and clinical oncology · 2024Review
- cAMP/PKA signaling regulates TDP-43 aggregation and mislocalization.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Integrative genetic analysis illuminates ALS heritability and identifies risk genes.Nature communications · 2023Article
- Posttranscriptional regulation of neurofilament proteins and tau in health and disease.Brain research bulletin · 2023Review
- Unraveling the impact of disrupted nucleocytoplasmic transport systems inFrontiers in cellular neuroscience · 2023Review
- Structure and Function of the Nuclear Pore Complex.Cold Spring Harbor perspectives in biology · 2022Review
- Regulating Phase Transition in Neurodegenerative Diseases by Nuclear Import Receptors.Biology · 2022Review
- Emerging Therapies and Novel Targets for TDP-43 Proteinopathy in ALS/FTD.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- Nuclear Pore Dysfunction in Neurodegeneration.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- Nuclear mRNA Export and Aging.International journal of molecular sciences · 2022Review
22 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 6 institutions in 2 countries.
Funding
Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective death of motor neurons. Causative mutations in the global RNA-processing proteins TDP-43 and FUS among others, as well as their aggregation in ALS patients, have identified defects in RNA metabolism as an important feature in this disease. Lethal congenital contracture syndrome 1 and lethal arthrogryposis with anterior horn cell disease are autosomal recessive fetal motor neuron diseases that are caused by mutations in another global RNA-processing protein, hGle1. In this study, we carried out the first screening of GLE1 in ALS patients (173 familial and 760 sporadic) and identified 2 deleterious mutations (1 splice site and 1 nonsense mutation) and 1 missense mutation. Functional analysis of the deleterious mutants revealed them to be unable to rescue motor neuron pathology in zebrafish morphants lacking Gle1. Furthermore, in HeLa cells, both mutations caused a depletion of hGle1 at the nuclear pore where it carries out an essential role in nuclear export of mRNA. These results suggest a haploinsufficiency mechanism and point to a causative role for GLE1 mutations in ALS patients. This further supports the involvement of global defects in RNA metabolism in ALS.
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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.