ArticleEMBO molecular medicine2013
Spliceosome integrity is defective in the motor neuron diseases ALS and SMA.
Article in EMBO molecular medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.
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Who cites it
120 citing papers in PubMed, 205 citations in OpenAlex.
- Intron retention in health and amyotrophic lateral sclerosis.Brain : a journal of neurology · 2026Review
- KIF5A downregulation in spinal muscular atrophy links axonal regeneration defects with ALS.JCI insight · 2026Article
- Maintenance and disruption of the physiological dimer structure of TDP-43 in amyotrophic lateral sclerosis and frontotemporal lobar degeneration.BMC medicine · 2026Review
- Understanding liquid-liquid phase separation through TDP-43: fundamental principles, subcellular compartmentalisation, and role of solid inclusion formation.Genome biology · 2026Review
- Neurodegenerative spliceosomopathies.Frontiers in cell and developmental biology · 2026Review
- RNA/DNA-binding protein TDP43 regulates DNA mismatch repair genes with implications for genome stability.Nucleic acids research · 2025Article
- Regulation of transcriptome plasticity by mTOR signaling pathway.Experimental & molecular medicine · 2025Review
- RNA/DNA Binding Protein TDP43 Regulates DNA Mismatch Repair Genes with Implications for Genome Stability.bioRxiv : the preprint server for biology · 2025Article
- The Role of Non-Coding RNAs in ALS.Genes · 2025Review
- The Regulation of TDP-43 Structure and Phase Transitions: A Review.The protein journal · 2025Review
- IL-1ra and CCL5, but not IL-10, are promising targets for treating SMA astrocyte-driven pathology.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Article
- SMN2 gene copy number affects the incidence and prognosis of motor neuron diseases in Japan.BMC medical genomics · 2024Article
- TDP-43 in nuclear condensates: where, how, and why.Biochemical Society transactions · 2024Review
- RNA-mediated ribonucleoprotein assembly controls TDP-43 nuclear retention.PLoS biology · 2024Article
- Nuclear-import receptors as gatekeepers of pathological phase transitions in ALS/FTD.Molecular neurodegeneration · 2024Review
- What could be the function of the spinal muscular atrophy-causing protein SMN in macrophages?Frontiers in immunology · 2024Review
- Transcriptome driven discovery of novel candidate genes for human neurological disorders in the telomer-to-telomer genome assembly era.Human genomics · 2023Article
- Analysis of asymptomatic Drosophila models for ALS and SMA reveals convergent impact on functional protein complexes linked to neuro-muscular degeneration.BMC genomics · 2023Article
- Loss of TDP-43 oligomerization or RNA binding elicits distinct aggregation patterns.The EMBO journal · 2023Article
60 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Two motor neuron diseases, amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), are caused by distinct genes involved in RNA metabolism, TDP-43 and FUS/TLS, and SMN, respectively. However, whether there is a shared defective mechanism in RNA metabolism common to these two diseases remains unclear. Here, we show that TDP-43 and FUS/TLS localize in nuclear Gems through an association with SMN, and that all three proteins function in spliceosome maintenance. We also show that in ALS, Gems are lost, U snRNA levels are up-regulated and spliceosomal U snRNPs abnormally and extensively accumulate in motor neuron nuclei, but not in the temporal lobe of FTLD with TDP-43 pathology. This aberrant accumulation of U snRNAs in ALS motor neurons is in direct contrast to SMA motor neurons, which show reduced amounts of U snRNAs, while both have defects in the spliceosome. These findings indicate that a profound loss of spliceosome integrity is a critical mechanism common to neurodegeneration in ALS and SMA, and may explain cell-type specific vulnerability of motor neurons.
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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.