ArticleThe EMBO journal2010
The splicing regulator Sam68 binds to a novel exonic splicing silencer and functions in SMN2 alternative splicing in spinal muscular atrophy.
Article in The EMBO journal, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
83 citing papers in PubMed, 141 citations in OpenAlex.
- Evaluation of SMN protein, transcript, and copy number in the biomarkers for spinal muscular atrophy (BforSMA) clinical study.PloS one · 2012Trial
- Transcriptome- and proteome-wide effects of a circular RNA encompassing four early exons of the spinal muscular atrophy genes.Scientific reports · 2024Article
- Sam68 is a druggable vulnerability point in cancer stem cells.Cancer metastasis reviews · 2024Review
- Transcriptome- and proteome-wide effects of a circular RNA encompassing four early exons of the spinal muscular atrophy genes.Research square · 2024Article
- Diverse targets of SMN2-directed splicing-modulating small molecule therapeutics for spinal muscular atrophy.Nucleic acids research · 2023Article
- The Role of Splicing Factors in Adipogenesis and Thermogenesis.Molecules and cells · 2023Review
- Structure and function analysis of Sam68 and hnRNP A1 synergy in the exclusion of exon 7 from SMN2 transcripts.Protein science : a publication of the Protein Society · 2023Article
- Gene Therapy in ALS and SMA: Advances, Challenges and Perspectives.International journal of molecular sciences · 2023Review
- Effects of Inhibitors of SLC9A-Type Sodium-Proton Exchangers onMolecular pharmacology · 2022Article
- Heat increases full-length SMN splicing: promise for splice-augmenting therapies for SMA.Human genetics · 2022Article
- Structural Context of a Critical Exon of Spinal Muscular Atrophy Gene.Frontiers in molecular biosciences · 2022Review
- Coordination of RNA Processing Regulation by Signal Transduction Pathways.Biomolecules · 2021Review
- Review
- The Importance of Digging into the Genetics ofInternational journal of molecular sciences · 2021Review
- A CRISPR RNA-binding protein screen reveals regulators of RUNX1 isoform generation.Blood advances · 2021Article
- Identification of SRSF10 as a regulator of SMN2 ISS-N1.Human mutation · 2021Article
- ITSN1 regulates SAM68 solubility through SH3 domain interactions with SAM68 proline-rich motifs.Cellular and molecular life sciences : CMLS · 2021Article
- SAM68 promotes tumorigenesis in lung adenocarcinoma by regulating metabolic conversion via PKM alternative splicing.Theranostics · 2021Article
- Article
- Alternative splicing in mesenchymal stem cell differentiation.Stem cells (Dayton, Ohio) · 2020Review
23 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by loss of motor neurons in patients with null mutations in the SMN1 gene. An almost identical SMN2 gene is unable to compensate for this deficiency because a single C-to-T transition at position +6 in exon-7 causes skipping of the exon by a mechanism not yet fully elucidated. We observed that the C-to-T transition in SMN2 creates a putative binding site for the RNA-binding protein Sam68. RNA pull-down assays and UV-crosslink experiments showed that Sam68 binds to this sequence. In vivo splicing assays showed that Sam68 triggers SMN2 exon-7 skipping. Moreover, mutations in the Sam68-binding site of SMN2 or in the RNA-binding domain of Sam68 completely abrogated its effect on exon-7 skipping. Retroviral infection of dominant-negative mutants of Sam68 that interfere with its RNA-binding activity, or with its binding to the splicing repressor hnRNP A1, enhanced exon-7 inclusion in endogenous SMN2 and rescued SMN protein expression in fibroblasts of SMA patients. Our results thus indicate that Sam68 is a novel crucial regulator of SMN2 splicing.
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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.