ArticleAmerican journal of human genetics2010
Correct mRNA processing at a mutant TT splice donor in FANCC ameliorates the clinical phenotype in patients and is enhanced by delivery of suppressor U1 snRNAs.
Article in American journal of human genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 60 citations in OpenAlex.
- Prenatal Diagnosis of a Fetus With Congenital Malformations Caused by Compound Heterozygous Mutations in FANCA: A Case Report and Literature Review.Molecular genetics & genomic medicine · 2026Review
- Clinical, cytogenetic, and molecular insights from 32 years of the Portuguese Fanconi anemia cohort.Genetics in medicine open · 2026Article
- RNA dysfunction in age-related macular degeneration: the role of U1 snRNP complex and neurodegenerative diseases.International journal of retina and vitreous · 2025Review
- In vitro model of retinoblastoma derived tumor and stromal cells for tumor microenvironment (TME) studies.Cell death & disease · 2024Article
- Role of Protein Tyrosine Phosphatase Receptor Type E (PTPRE) in Chemoresistant Retinoblastoma.International journal of molecular sciences · 2024Article
- New retinoblastoma (RB) drug delivery approaches: anti-tumor effect of atrial natriuretic peptide (ANP)-conjugated hyaluronic-acid-coated gold nanoparticles for intraocular treatment of chemoresistant RB.Molecular oncology · 2024Article
- FANCA c.3624C>T (p.Ser1208=) is a hypomorphic splice variant associated with delayed onset of Fanconi anemia.Blood advances · 2024Article
- Development of Engineered-U1 snRNA Therapies: Current Status.International journal of molecular sciences · 2023Review
- Tumor Suppressor Role of INPP4B in Chemoresistant Retinoblastoma.Journal of oncology · 2023Article
- ADAM10 and ADAM17-Novel Players in Retinoblastoma Carcinogenesis.International journal of molecular sciences · 2022Article
- Exon Skipping Through Chimeric AntisenseNucleic acid therapeutics · 2022Article
- Splicing Modulation as a Promising Therapeutic Strategy for Lysosomal Storage Disorders: The Mucopolysaccharidoses Example.Life (Basel, Switzerland) · 2022Review
- Role of L1CAM in retinoblastoma tumorigenesis: identification of novel therapeutic targets.Molecular oncology · 2022Article
- MRE11-dependent instability in mitochondrial DNA fork protection activates a cGAS immune signaling pathway.Science advances · 2021Article
- Profiling of cis- and trans-acting factors supporting noncanonical splice site activation.RNA biology · 2021Article
- Combining Engineered U1 snRNA and Antisense Oligonucleotides to Improve the Treatment of a BBS1 Splice Site Mutation.Molecular therapy. Nucleic acids · 2019Article
- p53, miR-34a and EMP1-Newly Identified Targets of TFF3 Signaling in Y79 Retinoblastoma Cells.International journal of molecular sciences · 2019Article
- Molecular Mechanisms and Determinants of Innovative Correction Approaches in Coagulation Factor Deficiencies.International journal of molecular sciences · 2019Review
- An Altered Splicing Registry Explains the Differential ExSpeU1-Mediated Rescue of Splicing Mutations Causing Haemophilia A.Frontiers in genetics · 2019Article
- Ranking noncanonical 5' splice site usage by genome-wide RNA-seq analysis and splicing reporter assays.Genome research · 2018Article
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Authors and funding
13 authors at 7 institutions in 3 countries.
Funding
Abstract
The U1 small nuclear RNA (U1 snRNA) as a component of the major U2-dependent spliceosome recognizes 5' splice sites (5'ss) containing GT as the canonical dinucleotide in the intronic positions +1 and +2. The c.165+1G>T germline mutation in the 5'ss of exon 2 of the Fanconi anemia C (FANCC) gene commonly predicted to prevent correct splicing was identified in nine FA patients from three pedigrees. RT-PCR analysis of the endogenous FANCC mRNA splicing pattern of patient-derived fibroblasts revealed aberrant mRNA processing, but surprisingly also correct splicing at the TT dinucleotide, albeit with lower efficiency. This consequently resulted in low levels of correctly spliced transcript and minute levels of normal posttranslationally processed FANCD2 protein, indicating that this naturally occurring TT splicing might contribute to the milder clinical manifestations of the disease in these patients. Functional analysis of this FANCC 5'ss within splicing reporters revealed that both the noncanonical TT dinucleotide and the genomic context of FANCC were required for the residual correct splicing at this mutant 5'ss. Finally, use of lentiviral vectors as a delivery system to introduce expression cassettes for TT-adapted U1 snRNAs into primary FANCC patient fibroblasts allowed the correction of the DNA-damage-induced G2 cell-cycle arrest in these cells, thus representing an alternative transcript-targeting approach for genetic therapy of inherited splice-site mutations.
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