ArticleHuman molecular genetics2008
hnRNP H enhances skipping of a nonfunctional exon P3A in CHRNA1 and a mutation disrupting its binding causes congenital myasthenic syndrome.
Article in Human molecular genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 60 citations in OpenAlex.
- SRSF6 and SRSF1 coordinately enhance the inclusion of humanNAR molecular medicine · 2025Article
- Evolutionarily Developed Alternatively Spliced Exons Containing Translation Initiation Sites.Cells · 2024Article
- Rbfox1 regulates alternative splicing of Nrcam in primary sensory neurons to mediate peripheral nerve injury-induced neuropathic pain.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- Splicing regulation of GFPT1 muscle-specific isoform and its roles in glucose metabolisms and neuromuscular junction.iScience · 2023Article
- Research Progress on the Structural and Functional Roles of hnRNPs in Muscle Development.Biomolecules · 2023Review
- Neural Isoforms of Agrin Are Generated by Reduced PTBP1-RNA Interaction Network Spanning the Neuron-Specific Splicing Regions inInternational journal of molecular sciences · 2023Article
- Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes-A Comprehensive Review.International journal of molecular sciences · 2023Review
- RNA Transcript Diversity in Neuromuscular Research.Journal of neuromuscular diseases · 2023Review
- Distinct roles of hnRNPH1 low-complexity domains in splicing and transcription.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- RNA Targeting in Inherited Neuromuscular Disorders: Novel Therapeutic Strategies to Counteract Mis-Splicing.Cells · 2021Review
- Heterogeneous Nuclear Ribonucleoproteins: Implications in Neurological Diseases.Molecular neurobiology · 2021Review
- [Congenital myasthenic syndromes in adulthood : Challenging, rare but treatable].Der Nervenarzt · 2019Review
- Profiling of patient-specific myocytes identifies altered gene expression in the ophthalmoplegic subphenotype of myasthenia gravis.Orphanet journal of rare diseases · 2019Article
- Specific G-quadruplex ligands modulate the alternative splicing of Bcl-X.Nucleic acids research · 2018Article
- SRSF1 suppresses selection of intron-distal 5' splice site of DOK7 intron 4 to generate functional full-length Dok-7 protein.Scientific reports · 2017Article
- Competitive regulation of alternative splicing and alternative polyadenylation by hnRNP H and CstF64 determines acetylcholinesterase isoforms.Nucleic acids research · 2017Article
- Protein and gene expression characteristics of heterogeneous nuclear ribonucleoprotein H1 in esophageal squamous cell carcinoma.World journal of gastroenterology · 2016Article
- The Splicing Efficiency of Activating HRAS Mutations Can Determine Costello Syndrome Phenotype and Frequency in Cancer.PLoS genetics · 2016Article
- Article
- SRSF1 and hnRNP H antagonistically regulate splicing of COLQ exon 16 in a congenital myasthenic syndrome.Scientific reports · 2015Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
In humans and great apes, CHRNA1 encoding the muscle nicotinic acetylcholine receptor alpha subunit carries an inframe exon P3A, the inclusion of which yields a nonfunctional alpha subunit. In muscle, the P3A(-) and P3A(+) transcripts are generated in a 1:1 ratio but the functional significance and regulation of the alternative splicing remain elusive. An intronic mutation (IVS3-8G>A), identified in a patient with congenital myasthenic syndrome, disrupts an intronic splicing silencer (ISS) and results in exclusive inclusion of the downstream P3A exon. We found that the ISS-binding splicing trans-factor was heterogeneous nuclear ribonucleoprotein (hnRNP) H and the mutation attenuated the affinity of hnRNP for the ISS approximately 100-fold. We next showed that direct placement of hnRNP H to the 3' end of intron 3 silences, and siRNA-mediated downregulation of hnRNP H enhances recognition of exon P3A. Analysis of the human genome suggested that the hnRNPH-binding UGGG motif is overrepresented close to the 3' ends of introns. Pursuing this clue, we showed that alternative exons of GRIP1, FAS, VPS13C and NRCAM are downregulated by hnRNP H. Our findings imply that the presence of the hnRNP H-binding motif close to the 3' end of an intron is an essential but underestimated splicing regulator of the downstream exon.
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