ArticleMolecular and cellular biology2012
A role for SMN exon 7 splicing in the selective vulnerability of motor neurons in spinal muscular atrophy.
Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 117 citations in OpenAlex.
- IndividualLife science alliance · 2026Article
- Specificity and exon target space of splicing modifying compounds.Nature communications · 2026Article
- A p53-ΔNp73 signaling axis drives selective motor neuron degeneration in spinal muscular atrophy.bioRxiv : the preprint server for biology · 2026Article
- Massively parallel assay of human splice variants reveals cis-regulatory drivers of disease-associated and cell type-specific splicing regulation.bioRxiv : the preprint server for biology · 2025Article
- Identification of p38 MAPK inhibition as a neuroprotective strategy for combinatorial SMA therapy.EMBO molecular medicine · 2025Article
- Patient-specific responses toMolecular therapy. Methods & clinical development · 2024Article
- Isogenic patient-derived organoids reveal early neurodevelopmental defects in spinal muscular atrophy initiation.Cell reports. Medicine · 2024Article
- Chaperoning the chaperones: Proteomic analysis of the SMN complex reveals conserved and etiologic connections to the proteostasis network.bioRxiv : the preprint server for biology · 2024Article
- Metabolomics of cerebrospinal fluid reveals candidate diagnostic biomarkers to distinguish between spinal muscular atrophy type II and type III.CNS neuroscience & therapeutics · 2024Article
- Proteomic analysis of the SMN complex reveals conserved and etiologic connections to the proteostasis network.Frontiers in RNA research · 2024Article
- Cerebellar structural, astrocytic, and neuronal abnormalities in the SMNΔ7 mouse model of spinal muscular atrophy.Brain pathology (Zurich, Switzerland) · 2023Article
- Evaluation of the orally bioavailable 4-phenylbutyrate-tethered trichostatin A analogue AR42 in models of spinal muscular atrophy.Scientific reports · 2023Article
- A spinal muscular atrophy modifier implicates the SMN protein in SNARE complex assembly at neuromuscular synapses.Neuron · 2023Article
- The SMN Complex at the Crossroad between RNA Metabolism and Neurodegeneration.International journal of molecular sciences · 2023Review
- Emerging Perspectives on Gene Therapy Delivery for Neurodegenerative and Neuromuscular Disorders.Journal of personalized medicine · 2022Review
- TGS1 impacts snRNA 3'-end processing, ameliorates survival motor neuron-dependent neurological phenotypes in vivo and prevents neurodegeneration.Nucleic acids research · 2022Article
- SMN controls neuromuscular junction integrity through U7 snRNP.Cell reports · 2022Article
- Spinal muscular atrophy.Nature reviews. Disease primers · 2022Review
- Bap1/SMN axis in Dpp4+ skeletal muscle mesenchymal cells regulates the neuromuscular system.JCI insight · 2022Article
- [Spinal muscular atrophy].Der Nervenarzt · 2022Article
19 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Spinal muscular atrophy (SMA) is an inherited motor neuron disease caused by homozygous loss of the Survival Motor Neuron 1 (SMN1) gene. In the absence of SMN1, inefficient inclusion of exon 7 in transcripts from the nearly identical SMN2 gene results in ubiquitous SMN decrease but selective motor neuron degeneration. Here we investigated whether cell type-specific differences in the efficiency of exon 7 splicing contribute to the vulnerability of SMA motor neurons. We show that normal motor neurons express markedly lower levels of full-length SMN mRNA from SMN2 than do other cells in the spinal cord. This is due to inefficient exon 7 splicing that is intrinsic to motor neurons under normal conditions. We also find that SMN depletion in mammalian cells decreases exon 7 inclusion through a negative feedback loop affecting the splicing of its own mRNA. This mechanism is active in vivo and further decreases the efficiency of exon 7 inclusion specifically in motor neurons of severe-SMA mice. Consistent with expression of lower levels of full-length SMN, we find that SMN-dependent downstream molecular defects are exacerbated in SMA motor neurons. These findings suggest a mechanism to explain the selective vulnerability of motor neurons to loss of SMN1.
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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.