ArticlePloS one2016
Oxidative Stress Triggers Body-Wide Skipping of Multiple Exons of the Spinal Muscular Atrophy Gene.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 46 citations in OpenAlex.
- Nusinersen: the antisense oligonucleotide at the forefront of spinal muscular atrophy treatment.RNA biology · 2026Review
- Pharmacological Activation of NRF2 by Omaveloxolone Upregulates NRF2-Target Proteins in SMA Type I Human Fibroblasts.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Review
- Genetic Variability in Oxidative Stress, Inflammatory, and Neurodevelopmental Pathways: Impact on the Susceptibility and Course of Spinal Muscular Atrophy.Cellular and molecular neurobiology · 2024Article
- Physiological Features of the Neural Stem Cells Obtained from an Animal Model of Spinal Muscular Atrophy and Their Response to Antioxidant Curcumin.International journal of molecular sciences · 2024Article
- A super minigene with a short promoter and truncated introns recapitulates essential features of transcription and splicing regulation of the SMN1 and SMN2 genes.Nucleic acids research · 2024Article
- U1 snRNA interactions with deep intronic sequences regulate splicing of multiple exons of spinal muscular atrophy genes.Frontiers in neuroscience · 2024Article
- Identification of pararosaniline as a modifier of RNA splicing in Caenorhabditis elegans.G3 (Bethesda, Md.) · 2023Article
- Induced alternative splicing an opportunity to study PCSK9 protein isoforms at physiologically relevant concentrations.Scientific reports · 2023Article
- Diverse targets of SMN2-directed splicing-modulating small molecule therapeutics for spinal muscular atrophy.Nucleic acids research · 2023Article
- Pathophysiology and Management of Fatigue in Neuromuscular Diseases.International journal of molecular sciences · 2023Review
- NSC Physiological Features in Spinal Muscular Atrophy: SMN Deficiency Effects on Neurogenesis.International journal of molecular sciences · 2022Review
- Mitochondrial Dysfunction in Spinal Muscular Atrophy.International journal of molecular sciences · 2022Review
- Revealing diverse alternative splicing variants of the highly homologous SMN1 and SMN2 genes by targeted long-read sequencing.Molecular genetics and genomics : MGG · 2022Article
- Internal Introns Promote Backsplicing to Generate Circular RNAs from Spinal Muscular Atrophy Gene.Genes · 2022Article
- Review
- High Concentration of an ISS-N1-Targeting Antisense Oligonucleotide Causes Massive Perturbation of the Transcriptome.International journal of molecular sciences · 2021Article
- Revisiting the role of mitochondria in spinal muscular atrophy.Cellular and molecular life sciences : CMLS · 2021Review
- Spinal muscular atrophy: Broad disease spectrum and sex-specific phenotypes.Biochimica et biophysica acta. Molecular basis of disease · 2021Review
- Characteristics of circular RNAs generated by human Survival Motor Neuron genes.Cellular signalling · 2020Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Humans carry two nearly identical copies of Survival Motor Neuron gene: SMN1 and SMN2. Loss of SMN1 leads to spinal muscular atrophy (SMA), the most frequent genetic cause of infant mortality. While SMN2 cannot compensate for the loss of SMN1 due to predominant skipping of exon 7, correction of SMN2 exon 7 splicing holds the promise of a cure for SMA. Previously, we used cell-based models coupled with a multi-exon-skipping detection assay (MESDA) to demonstrate the vulnerability of SMN2 exons to aberrant splicing under the conditions of oxidative stress (OS). Here we employ a transgenic mouse model and MESDA to examine the OS-induced splicing regulation of SMN2 exons. We induced OS using paraquat that is known to trigger production of reactive oxygen species and cause mitochondrial dysfunction. We show an overwhelming co-skipping of SMN2 exon 5 and exon 7 under OS in all tissues except testis. We also show that OS increases skipping of SMN2 exon 3 in all tissues except testis. We uncover several new SMN2 splice isoforms expressed at elevated levels under the conditions of OS. We analyze cis-elements and transacting factors to demonstrate the diversity of mechanisms for splicing misregulation under OS. Our results of proteome analysis reveal downregulation of hnRNP H as one of the potential consequences of OS in brain. Our findings suggest SMN2 as a sensor of OS with implications to SMA and other diseases impacted by low levels of SMN protein.
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