ArticleActa neuropathologica2022
Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis.
Article in Acta neuropathologica, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- What can we learn on ALS pathophysiology from iPSC-derived motor neurons harbouring TARBDP mutations: a systematic review.Translational neurodegeneration · 2026Pooled it
- An alternative splicing modulator decreases mutant HTT and improves the molecular fingerprint in Huntington's disease patient neurons.Nature communications · 2022Trial
- Decoding exon inclusion in the human brain reveals more divergent splicing mechanisms in neurons than glia.Genome biology · 2026Article
- Dominant-negative isoform of TDP-43 is regulated by ALS-linked RNA-binding proteins.The Journal of cell biology · 2025Article
- TDP-43 binds to RNA G-quadruplex structure and regulates mRNA stability and translation.Nucleic acids research · 2025Article
- RNA splicing modulator for Huntington's disease treatment induces peripheral neuropathy.iScience · 2025Article
- Localized molecular chaperone synthesis maintains neuronal dendrite proteostasis.Nature communications · 2024Article
- Article
- RNA splicing factor RBFOX2 is a key factor in the progression of cancer and cardiomyopathy.Clinical and translational medicine · 2024Review
- Identifying dysregulated regions in amyotrophic lateral sclerosis through chromatin accessibility outliers.HGG advances · 2024Article
- Homozygous ALS-linked mutations in TARDBP/TDP-43 lead to hypoactivity and synaptic abnormalities in human iPSC-derived motor neurons.iScience · 2024Article
- Alternative splicing and related RNA binding proteins in human health and disease.Signal transduction and targeted therapy · 2024Review
- Localized molecular chaperone synthesis maintains neuronal dendrite proteostasis.Research square · 2023Article
- Administration of A. muciniphila ameliorates pulmonary arterial hypertension by targeting miR-208a-3p/NOVA1 axis.Acta pharmacologica Sinica · 2023Article
- Interaction of theCells · 2023Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by aberrant alternative splicing (AS). Nuclear loss and cytoplasmic accumulation of the splicing factor TDP-43 in motor neurons (MN) are hallmarks of ALS at late stages of the disease. However, it is unknown if altered AS is present before TDP-43 pathology occurs. Here, we investigate altered AS and its origins in early stages of ALS using human induced pluripotent stem cell-derived motor neurons (MNs) from sporadic and familial ALS patients. We find high levels of the RNA-binding proteins NOVA1, NOVA2, and RBFOX2 in the insoluble protein fractions and observe that AS events in ALS-associated MNs are enriched for binding sites of these proteins. Our study points to an early disrupted function of NOVA1 that drives AS changes in a complex fashion, including events caused by a consistent loss of NOVA1 function. NOVA1 exhibits increased cytoplasmic protein levels in early stage MNs without TDP-43 pathology in ALS postmortem tissue. As nuclear TDP-43 protein level depletes, NOVA1 is reduced. Potential indications for a reduction of NOVA1 also came from mice over-expressing TDP-43 lacking its nuclear localization signal and iPSC-MN stressed with puromycin. This study highlights that additional RBP-RNA perturbations in ALS occur in parallel to TDP-43.
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