ArticleJCI insight2020
Minor snRNA gene delivery improves the loss of proprioceptive synapses on SMA motor neurons.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Dysregulation of U12-Type Splicing in Lupus Neutrophils.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- The survival motor neuron protein: structure, functions, stability, and therapeutic targeting.Frontiers in cellular neuroscience · 2026Review
- Dysregulation of U12-Type Splicing in Lupus Neutrophils.bioRxiv : the preprint server for biology · 2025Article
- Identification of p38 MAPK inhibition as a neuroprotective strategy for combinatorial SMA therapy.EMBO molecular medicine · 2025Article
- Stasimon/Tmem41b is required for cell proliferation and adult mouse survival.Biochemical and biophysical research communications · 2024Article
- Serotonergic dysfunction impairs locomotor coordination in spinal muscular atrophy.Brain : a journal of neurology · 2023Article
- The SMN Complex at the Crossroad between RNA Metabolism and Neurodegeneration.International journal of molecular sciences · 2023Review
- SMN post-translational modifications in spinal muscular atrophy.Frontiers in cellular neuroscience · 2023Review
- TGS1 impacts snRNA 3'-end processing, ameliorates survival motor neuron-dependent neurological phenotypes in vivo and prevents neurodegeneration.Nucleic acids research · 2022Article
- A link between agrin signalling and CaScientific reports · 2022Article
- SMN controls neuromuscular junction integrity through U7 snRNP.Cell reports · 2022Article
- Regulation of ER-derived membrane dynamics by the DedA domain-containing proteins VMP1 and TMEM41B.EMBO reports · 2022Review
- Neuromuscular denervation and deafferentation but not motor neuron death are disease features in the Smn2B/- mouse model of SMA.PloS one · 2022Article
- History of development of the life-saving drug "Nusinersen" in spinal muscular atrophy.Frontiers in cellular neuroscience · 2022Review
- Central synaptopathy is the most conserved feature of motor circuit pathology across spinal muscular atrophy mouse models.iScience · 2021Article
- Emerging concepts underlying selective neuromuscular dysfunction in infantile-onset spinal muscular atrophy.Neural regeneration research · 2021Review
- Spinal muscular atrophy: From approved therapies to future therapeutic targets for personalized medicine.Cell reports. Medicine · 2021Review
- Minor Intron Splicing from Basic Science to Disease.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder caused by reduced expression of the survival motor neuron (SMN) protein. SMN has key functions in multiple RNA pathways, including the biogenesis of small nuclear ribonucleoproteins that are essential components of both major (U2-dependent) and minor (U12-dependent) spliceosomes. Here we investigated the specific contribution of U12 splicing dysfunction to SMA pathology through selective restoration of this RNA pathway in mouse models of varying phenotypic severity. We show that virus-mediated delivery of minor snRNA genes specifically improves select U12 splicing defects induced by SMN deficiency in cultured mammalian cells, as well as in the spinal cord and dorsal root ganglia of SMA mice without increasing SMN expression. This approach resulted in a moderate amelioration of several parameters of the disease phenotype in SMA mice, including survival, weight gain, and motor function. Importantly, minor snRNA gene delivery improved aberrant splicing of the U12 intron-containing gene Stasimon and rescued the severe loss of proprioceptive sensory synapses on SMA motor neurons, which are early signatures of motor circuit dysfunction in mouse models. Taken together, these findings establish the direct contribution of U12 splicing dysfunction to synaptic deafferentation and motor circuit pathology in SMA.
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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.